Viruses

14 pages, 568 KiB

Open AccessArticle

Evaluation of Cognitive Functions in People Living with HIV Before and After COVID-19 Infection

by Dimtrios Basoulis, Elpida Mastrogianni, Irene Eliadi, Nikolaos Platakis, Dimitris Platis and Mina Psichogiou

Viruses 2025, 17(1), 135; https://doi.org/10.3390/v17010135 - 20 Jan 2025

Viewed by 490

Abstract

Background: Cognitive function decline is a problem in aging people living with HIV (PLWHIV). COVID-19 infection is associated with neuropsychiatric manifestations that may persist. The aim of our study was to evaluate cognitive function in PLWHIV before and after COVID-19 infection. Methods: This [...] Read more.

Background: Cognitive function decline is a problem in aging people living with HIV (PLWHIV). COVID-19 infection is associated with neuropsychiatric manifestations that may persist. The aim of our study was to evaluate cognitive function in PLWHIV before and after COVID-19 infection. Methods: This was a prospective observational study conducted at “Laiko” General Hospital from July 2019 to July 2024. The Montreal Cognitive Assessment (MOCA) scale was used to evaluate cognitive functions. Results: 116 virally suppressed PLWHIV participated (mean age: 47.6 years, 91.4% male); 60 underwent repeated evaluation after the pandemic at a median interval of 3.1 years. The median MOCA score was 24 (22–26), with 35.3% scoring within normal limits. A negative correlation was observed between MOCA scores and age (ρ = −0.283, p = 0.002), but not with a CD4 count at diagnosis (ρ = 0.169, p = 0.071) or initial HIV RNA load (ρ = 0.02, p = 0.984). In the subgroup with repeated testing, MOCA was correlated with the CD4 count (ρ = 0.238, p = 0.069 in the first and ρ = 0.319, p = 0.014 second test). An improvement in performance was observed (median score increase from 24 to 25, p = 0.02). Conclusions: MOCA can detect early changes in cognitive function in PLWHIV. Further studies are required to determine the role of COVID-19 over time. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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13 pages, 1925 KiB

Open AccessArticle

Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation

by Amanda Carroll-Portillo, October Barnes, Cristina N. Coffman, Cody A. Braun, Sudha B. Singh and Henry C. Lin

Viruses 2025, 17(1), 134; https://doi.org/10.3390/v17010134 - 19 Jan 2025

Viewed by 775

Abstract

Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the immune system through pathogen associated molecular pattern (PAMP) receptors (i.e., TLRs). [...] Read more.

Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the immune system through pathogen associated molecular pattern (PAMP) receptors (i.e., TLRs). Given that phages reside in the same body niches as bacteria, they share the propensity to stimulate or quench immune responses depending on the nature of their interactions with host immune cells. While most in vitro research focuses on the outcomes of direct application of phages to immune cells of interest, the potential impact of their transcytosis through the intestinal barrier has yet to be considered. As transcytosis through intestinal cells is a necessary step in healthy systems for access by phage to the underlying immune cell populations, it is imperative to understand how this step may play a role in immune activation. We compared the activation of macrophages (as measured by TNFα secretion) following direct phage application to those stimulated by incubation with phage transcytosed through a polarized Caco2 epithelial barrier model. Our results demonstrate that phages capable of activating TNFα secretion upon direct contact maintain the stimulatory capability following transcytosis. Furthermore, activation of macrophages by a transcytosed phage is enhanced as compared to that occurring with an equivalent multiplicity of directly applied phage. Full article

(This article belongs to the Section Bacterial Viruses)

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13 pages, 249 KiB

Open AccessReview

Herpesvirus Infections After Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies: A Review

by Joseph Sassine, Emily A. Siegrist and Roy F. Chemaly

Viruses 2025, 17(1), 133; https://doi.org/10.3390/v17010133 - 18 Jan 2025

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Abstract

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part [...] Read more.

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored. Clinically significant cytomegalovirus (CMV) infections can affect up to 10% of patients after CAR-T, depending on the CAR-T product target, post-CAR-T complications such as cytokine release syndrome and the need for glucocorticoid therapy. Surveillance and prophylactic strategies for CMV need to be developed, whereas the risk factors for and the burden of CMV infections after BsAb are not yet well-defined. Human herpes virus 6 reactivation and end organ disease such as encephalitis are rarely reported after CAR-T and have not yet been reported after BsAb; additional research is needed. Full article

(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)

15 pages, 1004 KiB

Open AccessReview

Interferon-Stimulated Genes and Immune Metabolites as Broad-Spectrum Biomarkers for Viral Infections

by Chien-Hsin Huang, Maudry Laurent-Rolle, Tyler L. Grove and Jack Chun-Chieh Hsu

Viruses 2025, 17(1), 132; https://doi.org/10.3390/v17010132 - 18 Jan 2025

Viewed by 831

Abstract

The type I interferon (IFN-I) response is a critical component of the immune defense against various viral pathogens, triggering the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs encode proteins with diverse antiviral functions, targeting various stages of viral replication and restricting [...] Read more.

The type I interferon (IFN-I) response is a critical component of the immune defense against various viral pathogens, triggering the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs encode proteins with diverse antiviral functions, targeting various stages of viral replication and restricting infection spread. Beyond their antiviral functions, ISGs and associated immune metabolites have emerged as promising broad-spectrum biomarkers that can differentiate viral infections from other conditions. This review provides an overview of the diagnostic potential of ISGs at transcript and protein levels, as well as their immune metabolites. We focus on their clinical applications and the sensitivity and specificity of these biomarkers through receiver operating characteristic (ROC) analysis. We highlight the need for further research to facilitate the effective translation of these biomarkers into clinical practice. Full article

(This article belongs to the Special Issue Molecular Biomarkers for Viral Infection)

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12 pages, 768 KiB

Open AccessBrief Report

Domestic Dogs Exposed to Orthopoxvirus in Urban Areas of Brazil

by Débora de Meneses, Ana G. Stoffella-Dutra, Vicenzo S. Blaso, Iara M. de Almeida, Karolina L. Dias, Iago José da S. Domingos, Gabriela P. Ribeiro, Wendel Coura-Vital, Alexandre B. Reis, Thallyta M. Vieira and Giliane de S. Trindade

Viruses 2025, 17(1), 131; https://doi.org/10.3390/v17010131 - 17 Jan 2025

Viewed by 602

Abstract

Domestic animals can share viral pathogens with humans, acting mainly as a bridge host. The Orthopoxvirus genus hosts important zoonotic species that have emerged in urban areas worldwide. Nevertheless, the role of companion animals, such as dogs and cats, in the circulation of [...] Read more.

Domestic animals can share viral pathogens with humans, acting mainly as a bridge host. The Orthopoxvirus genus hosts important zoonotic species that have emerged in urban areas worldwide. Nevertheless, the role of companion animals, such as dogs and cats, in the circulation of orthopoxviruses in urban areas remains poorly understood. Therefore, the objective of this study was to evaluate the presence of neutralizing anti-orthopoxvirus antibodies in serum samples from owned dogs from three municipalities in Minas Gerais, as well as the presence of the C11R and A56R orthopoxviruses genes. The presence of neutralizing antibodies was detected in 14.3% of the animals investigated. However, no sample was positive for the presence of the genes investigated. Further study of the population of dogs in urban areas may prove a valuable tool for understanding the spread of orthopoxviruses in urbanized areas of Brazil. Full article

(This article belongs to the Collection Poxviruses)

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13 pages, 551 KiB

Open AccessArticle

Eight Years of Norovirus Surveillance in Urban Wastewater: Insights from Next-Generation

by Giusy Bonanno Ferraro, David Brandtner, Pamela Mancini, Carolina Veneri, Marcello Iaconelli, Elisabetta Suffredini and Giuseppina La Rosa

Viruses 2025, 17(1), 130; https://doi.org/10.3390/v17010130 - 17 Jan 2025

Viewed by 754

Abstract

Human noroviruses (HNoVs) are a leading cause of acute gastroenteritis worldwide, with significant public health implications. In this study, wastewater-based epidemiology (WBE) was used to monitor the circulation and genetic diversity of HNoVs in Rome over an eight-year period (2017–2024). A total of [...] Read more.

Human noroviruses (HNoVs) are a leading cause of acute gastroenteritis worldwide, with significant public health implications. In this study, wastewater-based epidemiology (WBE) was used to monitor the circulation and genetic diversity of HNoVs in Rome over an eight-year period (2017–2024). A total of 337 wastewater samples were analyzed using RT-nested PCR and next-generation sequencing (NGS) to identify genogroups GI and GII and their respective genotypes. The results showed that GII had higher detection rates (66.5%) compared to GI (50.7%), with significant variation between years. Detection rates peaked in 2019 before declining sharply in 2020, coinciding with the COVID-19 pandemic and rebounding after the pandemic in 2023. A total of 24 genotypes were identified (8 GI and 17 GII), including persistent variants GII.2, GII.3 and GII.4 and emerging genotypes such as GII.8, GII.10 and GII.14. Only two GII.4 variants, Sydney_2016 and Sydney_2012, were detected in the study. These results demonstrate the utility of WBE in tracking HNoVs circulation, identifying genotype diversity and capturing shifts in transmission dynamics. WBE provides a cost-effective and comprehensive tool for public health surveillance, particularly in regions with limited clinical surveillance. Sustained investment in WBE is crucial for advancing our understanding of HNoVs epidemiology and its long-term trends. Full article

(This article belongs to the Special Issue Human Norovirus 2024)

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19 pages, 3797 KiB

Open AccessArticle

Optimization of Conditions for Expression of Dengue Serotype 2 EDIII Protein in Escherichia coli and Immune Responses of Adjuvant-Free EDIII Ferritin Nanoparticles Against Dengue Virus in BALB/c Mice

by M.S.B.W.T.M. Nipuna Sudaraka Tennakoon, Kyoung-Ho Lee, Hye-Mi Lee, Jae-Yeon Park and Hyun-Jin Shin

Viruses 2025, 17(1), 129; https://doi.org/10.3390/v17010129 - 17 Jan 2025

Viewed by 677

Abstract

Self-assembling ferritin nanoparticle technology is a widely used vaccine development platform for enhancing the efficacy of subunit vaccines by displaying multiple antigens on nanocages. The dengue virus (DENV) envelope domain III (EDIII) protein, the most promising antigen for DENV, has been applied in [...] Read more.

Self-assembling ferritin nanoparticle technology is a widely used vaccine development platform for enhancing the efficacy of subunit vaccines by displaying multiple antigens on nanocages. The dengue virus (DENV) envelope domain III (EDIII) protein, the most promising antigen for DENV, has been applied in vaccine development, and it is essential to evaluate the relative immunogenicity of the EDIII protein and EDIII-conjugated ferritin to show the efficiency of the ferritin delivery system compared with EDIII. In this study, we optimized the conditions for the expression of the EDIII protein in E. coli, protein purification, and refolding, and these optimization techniques were applied for the purification of EDIII ferritin nanoparticles. Thus, purified DENV2 EDIII and EDIII human ferritin heavy chain nanoparticles were immunized intramuscularly into BALB/c mice without an adjuvant, and the immunogenicity was analyzed using IgG ELISA and a serum-neutralizing assay. Purified, properly refolded, aggregate-free EDIII and EDIII ferritin proteins were obtained, and ferritin nanoparticles were identified using an electron microscope. By analyzing the immunogenicity of mouse serum, EDIII ferritin generated significantly higher IgG responses and neutralizing activity than EDIII-immunized mice. The IgG ELISA results confirmed that EDIII ferritin can induce a significantly higher IgG titer (O.D.:1.8) than EDIII (O.D.:0.05). Furthermore, EDIII ferritin produced a neutralizing titer of 1:68, whereas EDIII protein produced an average titer of 1:16, which is the serum dilution that inhibited 90% of the viruses. The longevity of the immune responses was analyzed using the serum obtained 2 months after the final immunization, and the results confirmed that EDIII ferritin induced constant immunity throughout the period. Full article

(This article belongs to the Special Issue Nanovaccines against Viral Infection)

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17 pages, 10291 KiB

Open AccessArticle

Screening of Insertion Sites and Tags on EV-A71 VP1 Protein for Recombinant Virus Construction

by Miaomiao Kang, Xiangyi Li, Xiaohong Li, Rui Yu, Shuo Zhang, Jingjing Yan, Xiaoyan Zhang, Jianqing Xu, Buyong Ma and Shuye Zhang

Viruses 2025, 17(1), 128; https://doi.org/10.3390/v17010128 - 17 Jan 2025

Viewed by 518

Abstract

This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and [...] Read more.

This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus’s infectivity and replication can be assessed by measuring postinfection luciferase signals. We reported that the site after the 100th amino acid within the VP1 BC loop of EV-A71 is particularly permissive for the insertion of various tags. Notably, the introduction of S and V5 tags at this position had minimal effect on the fitness of the tagged pseudovirus. Furthermore, recombinant infectious EV-A71 strains tagged with S and V5 epitopes were successfully rescued, and the stability of these tags was verified. Computational analysis suggested that viable insertions should be compatible with capsid assembly and receptor binding, whereas non-viable insertions could potentially disrupt the capsid’s binding with heparan sulfate. We expect the tagged recombinant EV-A71 to be a useful tool for studying the various stages of the enterovirus life cycle and for virus purification, immunoprecipitation, and research in immunology and vaccine development. Furthermore, this study serves as a proof of principle and may help develop similar tags in enteroviruses, for which there are fewer available tools. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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19 pages, 1036 KiB

Open AccessReview

Additive Effects of Glutathione in Improving Antibiotic Efficacy in HIV–M.tb Co-Infection in the Central Nervous System: A Systematic Review

by Leena Nabipur, Michael Mouawad and Vishwanath Venketaraman

Viruses 2025, 17(1), 127; https://doi.org/10.3390/v17010127 - 17 Jan 2025

Viewed by 678

Abstract

Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. [...] Read more.

Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. Glutathione (GSH) has the therapeutic potential to enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, and mitigating immune dysfunction. Methods: Relevant studies were identified through systematic searches of PubMed, Elsevier, WHO, and related databases. Inclusion criteria focused on preclinical and clinical research examining GSH or its precursors in HIV, TB, or co-infection, with emphasis on microbial control, immune modulation, and CNS-related outcomes. Results: Preclinical studies showed that GSH improves macrophage antimicrobial function, reduces oxidative stress, and limits Mycobacterium tuberculosis (M.tb) growth. Animal models demonstrated reduced bacterial burden in the lungs, liver, and spleen with GSH supplementation, along with enhanced granuloma stability. Clinical studies highlighted increased TH1 cytokine production, reduced inflammatory markers, and improved CD4+ T cell counts in HIV–M.tb co-infected patients. N-acetylcysteine (NAC), a GSH precursor, was shown to significantly enhance the efficacy of first-line TB antibiotics and mitigate treatment-associated toxicity. Discussion: GSH shows promise as an adjunct therapy for HIV–M.tb co-infection, particularly for cases involving the CNS, where it may improve immune recovery and reduce inflammation. However, evidence is limited by small sample sizes and a lack of randomized trials. Future research should focus on developing CNS-directed GSH formulations and evaluating its integration into current treatment protocols to address the dual burden of HIV and TB, ultimately improving patient outcomes. Full article

(This article belongs to the Special Issue HIV and Tuberculosis (TB) Coinfection)

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17 pages, 2102 KiB

Open AccessArticle

High-Throughput Oxford Nanopore Sequencing Unveils Complex Viral Population in Kansas Wheat: Implications for Sustainable Virus Management

by Nar B. Ranabhat, John P. Fellers, Myron A. Bruce and Jessica L. Shoup Rupp

Viruses 2025, 17(1), 126; https://doi.org/10.3390/v17010126 - 17 Jan 2025

Viewed by 536

Abstract

Wheat viruses are major yield-reducing factors, with mixed infections causing substantial economic losses. Determining field virus populations is crucial for effective management and developing virus-resistant cultivars. This study utilized the high-throughput Oxford Nanopore sequencing technique (ONT) to characterize wheat viral populations in major [...] Read more.

Wheat viruses are major yield-reducing factors, with mixed infections causing substantial economic losses. Determining field virus populations is crucial for effective management and developing virus-resistant cultivars. This study utilized the high-throughput Oxford Nanopore sequencing technique (ONT) to characterize wheat viral populations in major wheat-growing counties of Kansas from 2019 to 2021. Wheat leaves exhibiting virus-like symptoms were collected, total RNA was extracted, and cDNA libraries were prepared using a PCR-cDNA barcoding kit, then loaded onto ONT MinION flow cells. Sequencing reads aligned with cereal virus references identified eight wheat virus species. Tritimovirus tritici (wheat streak mosaic virus, WSMV), Poacevirus tritici (Triticum mosaic virus, TriMV), Bromovirus BMV (brome mosaic virus, BMV), as well as Emaravirus tritici, Luteovirus pavhordei, L. sgvhordei, Bymovirus tritici, and Furovirus tritici. Mixed infections involving two to five viruses in a single sample were common, with the most prevalent being WSMV + TriMV at 16.7% and WSMV + TriMV + BMV at 11.9%. Phylogenetic analysis revealed a wide distribution of WSMV isolates, including European and recombinant variants. A phylogenetic analysis of Emaravirus tritici based on RNA 3A and 3B segments and whole-genome characterization of Furovirus tritici were also conducted. These findings advance understanding of genetic variability, phylogenetics, and viral co-infections, supporting the development of sustainable management practices through host genetic resistance. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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11 pages, 615 KiB

Open AccessArticle

Low-Level Zoonotic Transmission of Clade C MERS-CoV in Africa: Insights from Scoping Review and Cohort Studies in Hospital and Community Settings

by Andrew Karani, Cynthia Ombok, Silvia Situma, Robert Breiman, Marianne Mureithi, Walter Jaoko, M. Kariuki Njenga and Isaac Ngere

Viruses 2025, 17(1), 125; https://doi.org/10.3390/v17010125 - 17 Jan 2025

Viewed by 570

Abstract

Human outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) are more common in Middle Eastern and Asian human populations, associated with clades A and B. In Africa, where clade C is dominant in camels, human cases are minimal. We reviewed 16 studies (n [...] Read more.

Human outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) are more common in Middle Eastern and Asian human populations, associated with clades A and B. In Africa, where clade C is dominant in camels, human cases are minimal. We reviewed 16 studies (n = 6198) published across seven African countries between 2012 and 2024 to assess human MERS-CoV cases. We also analyzed data from four cohort studies conducted in camel-keeping communities between 2018 and 2024 involving camel keepers, camel slaughterhouse workers, and hospital patients with acute respiratory illness (ARI). The analysis showed a pooled MERS-CoV prevalence of 2.4% (IQR: 0.6, 11.4) from 16 publications and 1.14% from 4 cohort studies (n = 2353). Symptomatic cases were rarely reported, with most individuals reporting camel contact, and only 12% had travel history to the Middle East. There was one travel-associated reported death, resulting in a mortality rate of 0.013%. The findings suggest a low camel-to-human transmission of clade C MERS-CoV in Africa. Ongoing research focuses on genomic comparisons between clade C and the more virulent clades A and B, alongside the surveillance of viral evolution. This study highlights the need for continuous monitoring but indicates that MERS-CoV clade C currently poses a minimal public health threat in Africa. Full article

(This article belongs to the Section Coronaviruses)

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21 pages, 400 KiB

Open AccessReview

Dynamic Roles of RNA and RNA Epigenetics in HTLV-1 Biology

by Emily M. King and Amanda R. Panfil

Viruses 2025, 17(1), 124; https://doi.org/10.3390/v17010124 - 17 Jan 2025

Viewed by 1028

Abstract

Since the discovery of RNA in the early 1900s, scientific understanding of RNA form and function has evolved beyond protein coding. Viruses, particularly retroviruses like human T-cell leukemia virus type 1 (HTLV-1), rely heavily on RNA and RNA post-transcriptional modifications to regulate the [...] Read more.

Since the discovery of RNA in the early 1900s, scientific understanding of RNA form and function has evolved beyond protein coding. Viruses, particularly retroviruses like human T-cell leukemia virus type 1 (HTLV-1), rely heavily on RNA and RNA post-transcriptional modifications to regulate the viral lifecycle, pathogenesis, and evasion of host immune responses. With the emergence of new sequencing technologies in the last decade, our ability to dissect the intricacies of RNA has flourished. The ability to study RNA epigenetic modifications and splice variants has become more feasible with the recent development of third-generation sequencing technologies, such as Oxford nanopore sequencing. This review will highlight the dynamic roles of known RNA and post-transcriptional RNA epigenetic modifications within HTLV-1 biology, including viral hbz, long noncoding RNAs, microRNAs (miRNAs), transfer RNAs (tRNAs), R-loops, N6-methyladenosine (m⁶A) modifications, and RNA-based therapeutics and vaccines. Full article

(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)

6 pages, 587 KiB

Open AccessCase Report

Phage Therapy as a Rescue Treatment for Recurrent Pseudomonas aeruginosa Bentall Infection

by Victor Eiferman, Pierre-Adrien Vion and Alexandre Bleibtreu

Viruses 2025, 17(1), 123; https://doi.org/10.3390/v17010123 - 17 Jan 2025

Viewed by 583

Abstract

Phage therapy is experiencing renewed interest, particularly for antibiotic-resistant infections, and may also be useful for difficult-to-treat cases where surgery to remove foreign infected material is deemed too risky. We report a case of recurrent Pseudomonas aeruginosa endocarditis with Bentall infection treated successfully [...] Read more.

Phage therapy is experiencing renewed interest, particularly for antibiotic-resistant infections, and may also be useful for difficult-to-treat cases where surgery to remove foreign infected material is deemed too risky. We report a case of recurrent Pseudomonas aeruginosa endocarditis with Bentall infection treated successfully with a combination of antibiotics and phages. Full article

(This article belongs to the Special Issue Phage Cocktails: Promising Approaches Against Infections)

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16 pages, 8085 KiB

Open AccessArticle

Neurotropic Tick-Borne Flavivirus in Alpine Chamois (Rupicapra rupicapra rupicapra), Austria, 2017, Italy, 2023

by Norbert Nowotny, Maria Lucia Mandola, Isabella Monne, Zoltán Bagó, Chiara Nogarol, Alice Fusaro, Katharina Dimmel, Barbara Moroni, Lisa Guardone, Jolanta Kolodziejek, Elisa Palumbo, Gabriela Stanclova, Adi Steinrigl, Gabriele Fidler, Cristina Bertasio, Irene Bertoletti, Alessandro Bianchi, Mattia Calzolari, Paola Prati, Nadia Vicari, Angela Salomoni, Maria Francesca Priore, Federica Gobbo, Aitor Garcia-Vozmediano, Tom Loney, Ahmad Abou Tayoun, Alawi Alsheikh-Ali, Paola De Benedictis, Jeremy V. Camp, Zdenek Hubalek, Ivo Rudolf, Davide Lelli and Ana Moreno Show full author list Hide full author list

Viruses 2025, 17(1), 122; https://doi.org/10.3390/v17010122 - 16 Jan 2025

Viewed by 1106

Abstract

The European subtype of tick-borne encephalitis virus (TBEV-Eur; species Orthoflavivirus encephalitidis, family Flaviviridae) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from [...] Read more.

The European subtype of tick-borne encephalitis virus (TBEV-Eur; species Orthoflavivirus encephalitidis, family Flaviviridae) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from Alpine chamois (Rupicapra rupicapra rupicapra) with encephalitis and attached ticks, present over a wide area in the Alps. Cases were detected in 2017 in Salzburg, Austria, and 2023 in Lombardy and Piedmont, Italy. The virus strains exhibit 94.8–97.3% nucleotide identities to each other and are more closely related to Louping ill viruses (LIV; Orthoflavivirus loupingi; 90–92% identities) than to TBEV-Eur (less than 88%). The chamois-derived virus strains, tentatively termed “Alpine chamois encephalitis virus”, form a well-supported independent genetic clade with Spanish goat encephalitis virus, clearly separated from other LIV. This supports its designation as a new virus subtype with the proposed shared taxonomic name “Spanish goat and Alpine chamois encephalitis virus subtype” within the species Orthoflavivirus loupingi. The zoonotic potential of this newly identified virus subtype as well as its host range in other animal species including farm animals needs to be further investigated. Full article

(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance, 2nd Edition)

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10 pages, 867 KiB

Open AccessArticle

Comparative Analyses of Antiviral Potencies of Second-Generation Integrase Strand Transfer Inhibitors (INSTIs) and the Developmental Compound 4d Against a Panel of Integrase Quadruple Mutants

by Steven J. Smith, Xue Zhi Zhao, Stephen H. Hughes and Terrence R. Burke, Jr.

Viruses 2025, 17(1), 121; https://doi.org/10.3390/v17010121 - 16 Jan 2025

Viewed by 526

Abstract

Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs [...] Read more.

Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance. Herein, we evaluated the antiviral potencies of our lead developmental INSTI 4d and the second-generation INSTIs dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) against a panel of IN quadruple mutants. The mutations are centered around G140S/Q148H, including positions L74, E92, and T97 combined with E138A/K/G140S/Q148H. All of the tested INSTIs lose potency against these IN quadruple mutants compared with the wild-type IN. In single-round infection assays, compound 4d retained higher antiviral potencies (EC₅₀ values) than second-generation INSTIs against a subset of quadruple mutants. These findings may advance understanding of mechanisms that contribute to resistance and, in so doing, facilitate development of new INSTIs with improved antiviral profiles. Full article

(This article belongs to the Collection Efficacy and Safety of Antiviral Therapy)

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24 pages, 6076 KiB

Open AccessArticle

Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines

by David M. Renner, Nicholas A. Parenti, Nicole Bracci and Susan R. Weiss

Viruses 2025, 17(1), 120; https://doi.org/10.3390/v17010120 - 16 Jan 2025

Viewed by 632

Abstract

The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus—HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)—, to study betacoronavirus interactions [...] Read more.

The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus—HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)—, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation. We demonstrate that MERS-CoV, HCoV-OC43, and SARS-CoV-2 all activate PERK and induce responses downstream of p-eIF2α, while only SARS-CoV-2 induces detectable p-eIF2α during infection. Using a small molecule inhibitor of eIF2α dephosphorylation, we provide evidence that MERS-CoV and HCoV-OC43 maximize viral replication through p-eIF2α dephosphorylation. Interestingly, genetic ablation of growth arrest and DNA damage-inducible protein (GADD34) expression, an inducible protein phosphatase 1 (PP1)-interacting partner targeting eIF2α for dephosphorylation, did not significantly alter HCoV-OC43 or SARS-CoV-2 replication, while siRNA knockdown of the constitutive PP1 partner, constitutive repressor of eIF2α phosphorylation (CReP), dramatically reduced HCoV-OC43 replication. Combining GADD34 knockout with CReP knockdown had the maximum impact on HCoV-OC43 replication, while SARS-CoV-2 replication was unaffected. Overall, we conclude that eIF2α dephosphorylation is critical for efficient protein production and replication during MERS-CoV and HCoV-OC43 infection. SARS-CoV-2, however, appears to be insensitive to p-eIF2α and, during infection, may even downregulate dephosphorylation to limit host translation. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals)

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14 pages, 518 KiB

Open AccessArticle

Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

by Francesco Drago, Astrid Herzum, Serena Varesano, Gaetano Serviddio, Francesco Broccolo and Giulia Ciccarese

Viruses 2025, 17(1), 119; https://doi.org/10.3390/v17010119 - 16 Jan 2025

Viewed by 513

Abstract

Pityriasis rosea (PR) is a self-limited exanthem associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and HHV-7. The disease typically begins with a single erythematous patch on the trunk (herald patch), followed by a secondary eruption of smaller papulosquamous lesions. Rarely, [...] Read more.

Pityriasis rosea (PR) is a self-limited exanthem associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and HHV-7. The disease typically begins with a single erythematous patch on the trunk (herald patch), followed by a secondary eruption of smaller papulosquamous lesions. Rarely, the herald patch may be the only cutaneous manifestation of PR. The present work aimed to examine the clinical and laboratory features of the PR cases characterized by the herald patch as the sole cutaneous manifestation and to compare them with the classic form of PR. An observational, retrospective study was conducted on patients presenting with herald patch as the only sign of PR (cases) and on a series of age- and sex-matched patients who presented with a typical PR pattern (controls). The records of the patients were extracted from a PR registry, which collected data on patients with PR diagnosed from 2003 to 2023 by at least two dermatologists from the same study team. Nineteen patients (eleven males, eight females) with a mean age of 27.1 years presented the herald patch as the only cutaneous manifestation of PR. Nineteen age- and sex-matched patients were considered controls. In the cases, the exanthem duration was shorter than in controls, and the mean HHV-6 and HHV-7 DNA plasma load was lower than in controls. This rare variant of PR might be considered an abortive form of the exanthem that occurs when the HHV-6/7 reactivation from latency is contrasted by a more robust immunological response than in classic PR. Full article

(This article belongs to the Special Issue Innate and Adaptive Immunity to Cutaneous Virus Infection)

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19 pages, 3613 KiB

Open AccessReview

Gene Therapy for Glioblastoma Multiforme

by Smit Shah, Joshua Green, Shantelle A. Graff, Qi Li and John D. Heiss

Viruses 2025, 17(1), 118; https://doi.org/10.3390/v17010118 - 16 Jan 2025

Viewed by 598

Abstract

Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood–brain barrier, drug resistance, and complex genetic tumor alterations. [...] Read more.

Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood–brain barrier, drug resistance, and complex genetic tumor alterations. Gene therapy uses a mechanism different from other GBM therapies to reduce tumor growth and enhance antitumor immunity. This review article will provide an update on various viral and nonviral vectors, their DNA and RNA cargoes, and how they genetically modify tumor cells and evoke therapeutic responses to GBM. The article explores the oncolytic and immunogenic effects of gene therapy agents. It reviews promising DNA transgenes, RNA inhibitors, and vectors for anti-GBM therapy. The possible benefits of combining gene therapy with standard GBM treatments will also be covered. Full article

(This article belongs to the Section General Virology)

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22 pages, 4211 KiB

Open AccessArticle

Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses

by Chukwudi A. Ofodile, Ikemefuna C. Uzochukwu, Fortunatus C. Ezebuo, InnocentMary Ejiofor, Mercy Adebola, Innocent Okpoli, Beatrice Cubitt, Haydar Witwit, Chetachi B. Okwuanaso, Ngozi Onyemelukwe and Juan Carlos de la Torre

Viruses 2025, 17(1), 117; https://doi.org/10.3390/v17010117 - 16 Jan 2025

Viewed by 518

Abstract

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence [...] Read more.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome. Validation of docking protocols were achieved with reference inhibitors of the respective targets. Our in silico docking screen identified five drugs (dexamethasone, tadalafil, mefloquine, ergocalciferol, and flunarizine) with strong predicted binding affinity to LASV proteins involved in the formation of the vRNP. We used cell-based functional assays to evaluate the antiviral activity of the five selected drugs. We found that flunarizine, a calcium-entry blocker, inhibited the vRNP activity of LASV and LCMV and virus surface glycoprotein fusion activity required for mammarenavirus cell entry. Consistently with these findings, flunarizine significantly reduced peak titers of LCMV in a multi-step growth kinetics assay in human A549 cells. Flunarizine is being used in several countries worldwide to treat vertigo and migraine, supporting the interest in exploring its repurposing as a candidate drug to treat LASV infections. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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12 pages, 1908 KiB

Open AccessArticle

Enhanced Immunogenicity and Affinity with A35R-Fc-Based Chimeric Protein Compared to MPXV A35R Protein

by Shimeng Bai, Yanxin Cui, Qibin Liao, Hongyang Yi, Zhonghui Liao, Gengwei Zhang, Fenfang Wu and Hongzhou Lu

Viruses 2025, 17(1), 116; https://doi.org/10.3390/v17010116 - 16 Jan 2025

Viewed by 474

Abstract

The re-emergence of the mpox pandemic poses considerable challenges to human health and societal development. There is an urgent need for effective prevention and treatment strategies against the mpox virus (MPXV). In this study, we focused on the A35R protein and created a [...] Read more.

The re-emergence of the mpox pandemic poses considerable challenges to human health and societal development. There is an urgent need for effective prevention and treatment strategies against the mpox virus (MPXV). In this study, we focused on the A35R protein and created a chimeric A35R-Fc protein by fusing the Fc region of IgG to its C-terminal. We then assessed its reactivity with A35R-specific antibodies and human convalescent plasma, as well as its immunogenicity. Our findings indicate that the A35R-Fc protein significantly enhances affinity to A35R antibodies compared to the commercially available A35R protein and exhibits considerable reactivity to human plasma. Additionally, mice immunized with A35R-Fc exhibited increased neutralizing antibody titers against the live MPXV. These results support the potential of Fc domain chimeric antigens as a strategy to enhance the efficacy of subunit vaccines targeting the MPXV. Full article

(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)

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16 pages, 2236 KiB

Open AccessArticle

Klebsiella pneumoniae Phage M198 and Its Therapeutic Potential

by Lika Leshkasheli, Ia Kusradze, Darejan Bolkvadze, Lia Askilashvili, Maria Chichashvili, Giorgi Tsertsvadze and Elisabed Zaldastanishvili

Viruses 2025, 17(1), 115; https://doi.org/10.3390/v17010115 - 15 Jan 2025

Viewed by 490

Abstract

The rapid worldwide spread of antibiotic resistance is quickly becoming an increasingly concerning problem for human healthcare. Non-antibiotic antibacterial agents are in high demand for many Gram-negative bacterial pathogens, including Klebsiella pneumoniae. Klebsiella-targeting phages are among the most promising alternative therapy [...] Read more.

The rapid worldwide spread of antibiotic resistance is quickly becoming an increasingly concerning problem for human healthcare. Non-antibiotic antibacterial agents are in high demand for many Gram-negative bacterial pathogens, including Klebsiella pneumoniae. Klebsiella-targeting phages are among the most promising alternative therapy options. They have already been successfully applied in a number of cases, and it is expected that the need for anti-Klebsiella phages will only increase in the future. This prospect highlights the need for well-characterized therapeutic phages. In this work, we describe a K. pneumoniae phage, which also infects strains of Klebsiella oxytoca. Here, we characterize phage M198 in terms of its biological and genetic properties. Since in some phage therapy cases, phages are administered in combination with antibiotics, here, we also screen for possible synergistic effects of combining phage M198 with six different antibiotics. We found that phage M198 has good lytic activity against clinical isolates; it does not have any indications of a temperate lifestyle, and it has synergistic potential when combined with some therapeutically relevant antibiotics. Full article

(This article belongs to the Collection Phage Therapy)

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13 pages, 2108 KiB

Open AccessArticle

Genomic, Evolutionary, and Pathogenic Characterization of a New Polerovirus in Traditional Chinese Medicine Viola philippica

by Yuanling Chen, Gaoxiang Chen, Jiaping Yu, Yali Zhou, Shifang Fei, Haorong Chen, Jianxiang Wu and Shuai Fu

Viruses 2025, 17(1), 114; https://doi.org/10.3390/v17010114 - 15 Jan 2025

Viewed by 466

Abstract

Viola philippica, a medicinal herbaceous plant documented in the Chinese Pharmacopoeia, is a promising candidate for research into plant-derived pharmaceuticals. However, the study of newly emerging viruses that threaten the cultivation of V. philippica remains limited. In this study, V. philippica plants [...] Read more.

Viola philippica, a medicinal herbaceous plant documented in the Chinese Pharmacopoeia, is a promising candidate for research into plant-derived pharmaceuticals. However, the study of newly emerging viruses that threaten the cultivation of V. philippica remains limited. In this study, V. philippica plants exhibiting symptoms such as leaf yellowing, mottled leaves, and vein chlorosis were collected and subjected to RNA sequencing to identify potential viral pathogens. A novel polerovirus, named Viola Philippica Polerovirus (VPPV), was identified in V. philippica. VPPV possesses a linear, positive-sense, single-stranded RNA genome consisting of 5535 nucleotides (nt) and encodes seven highly overlapping open reading frames (ORFs). Two potential recombination events were identified within ORF2, ORF3a, and ORF3, providing insights into the genetic diversity and evolution history of this novel polerovirus. An infectious cDNA clone of VPPV was successfully constructed and shown to infect Nicotiana benthamiana. Using a PVX-based heterologous expression system, the VPPV P0 protein was shown to trigger a systemic hypersensitive response (HR)-like reaction in N. benthamiana, indicating that P0 functions as the main pathogenicity determinant. These findings contributed to the detection and understanding of pathogenic mechanisms and control strategies for VPPV in V. philippica. Full article

(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)

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18 pages, 4160 KiB

Open AccessArticle

Expanding the Diversity of Actinobacterial Tectiviridae: A Novel Genus from Microbacterium

by Jacqueline M. Washington, Holly Basta, Angela Bryanne De Jesus, Madison G. Bendele, Steven G. Cresawn and Emily K. Ginser

Viruses 2025, 17(1), 113; https://doi.org/10.3390/v17010113 - 15 Jan 2025

Viewed by 574

Abstract

Six novel Microbacterium phages belonging to the Tectiviridae family were isolated using Microbacterium testaceum as a host. Phages MuffinTheCat, Badulia, DesireeRose, Bee17, SCoupsA, and LuzDeMundo were purified from environmental samples by students participating in the Science Education Alliance Phage Hunters Advancing Genomics and [...] Read more.

Six novel Microbacterium phages belonging to the Tectiviridae family were isolated using Microbacterium testaceum as a host. Phages MuffinTheCat, Badulia, DesireeRose, Bee17, SCoupsA, and LuzDeMundo were purified from environmental samples by students participating in the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program at Alliance University, New York. The phages have linear dsDNA genomes 15,438–15,636 bp with 112–120 bp inverted terminal repeats. Transmission electron microscopy (TEM) imaging analysis revealed that the six novel phages have six-sided icosahedral double-layered capsids with an internal lipid membrane that occasionally forms protruding nanotubules. Annotation analysis determined that the novel Microbacterium phages all have 32–34 protein-coding genes and no tRNAs. Like other Tectiviridae, the phage genomes are arranged into two segments and include three highly conserved family genes that encode a DNA polymerase, double jelly-roll major capsid protein, and packaging ATPase. Although the novel bacteriophages have 91.6 to 97.5% nucleotide sequence similarity to each other, they are at most 58% similar to previously characterized Tectiviridae genera. Consequently, these novel Microbacterium phages expand the diversity of the Tectiviridae family, and we propose they form the sixth genus, Zetatectivirus. Full article

(This article belongs to the Special Issue Bacteriophage Diversity)

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15 pages, 1965 KiB

Open AccessArticle

Inovirus-Encoded Peptides Induce Specific Toxicity in Pseudomonas aeruginosa

by Juehua Weng, Yunxue Guo, Jiayu Gu, Ran Chen and Xiaoxue Wang

Viruses 2025, 17(1), 112; https://doi.org/10.3390/v17010112 - 15 Jan 2025

Viewed by 569

Abstract

Pseudomonas aeruginosa is a common opportunistic pathogen associated with nosocomial infections. The primary treatment for infections typically involves antibiotics, which can lead to the emergence of multidrug-resistant strains. Therefore, there is a pressing need for safe and effective alternative methods. Phage therapy stands [...] Read more.

Pseudomonas aeruginosa is a common opportunistic pathogen associated with nosocomial infections. The primary treatment for infections typically involves antibiotics, which can lead to the emergence of multidrug-resistant strains. Therefore, there is a pressing need for safe and effective alternative methods. Phage therapy stands out as a promising approach. However, filamentous prophages (Pfs) commonly found in P. aeruginosa encode genes with phage defense activity, thereby reducing the efficacy of phage therapy. Through a genomic analysis of the Pf4 prophage, we identified a 102 bp gene co-transcribed with the upstream gene responsible for phage release (zot gene), giving rise to a 33-amino-acid polypeptide that we have named Pf4-encoded toxic polypeptide (PftP4). The overexpression of PftP4 demonstrated cellular toxicity in P. aeruginosa, with subcellular localization indicating its presence in the cell membrane and a subsequent increase in membrane permeability. Notably, PftP4 homologues are found in multiple Pf phages and exhibit specificity in their toxicity towards P. aeruginosa among the tested bacterial strains. Our study reveals that the novel Pf-encoded polypeptide PftP4 has the potential to selectively target and eradicate P. aeruginosa, offering valuable insights for combating P. aeruginosa infections. Full article

(This article belongs to the Special Issue Inoviruses)

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12 pages, 559 KiB

Open AccessArticle

Clinical Features of Human Parvovirus B19-Associated Encephalitis Identified in the Dakar Region, Senegal, and Viral Genome Characterization

by Al Ousseynou Seye, Fatou Kiné Top, Maimouna Mbanne, Moussa Moise Diagne, Ousmane Faye, Amadou Alpha Sall, Ndongo Dia, Jean-Michel Heraud and Martin Faye

Viruses 2025, 17(1), 111; https://doi.org/10.3390/v17010111 - 15 Jan 2025

Viewed by 698

Abstract

Neurological manifestations associated with human parvovirus B19 (B19V) infections are rare and varied. Acute encephalitis and encephalopathy are the most common, accounting for 38.8% of all neurological manifestations associated with human B19V. Herein, we report on the clinical features of 13 laboratory-confirmed human [...] Read more.

Neurological manifestations associated with human parvovirus B19 (B19V) infections are rare and varied. Acute encephalitis and encephalopathy are the most common, accounting for 38.8% of all neurological manifestations associated with human B19V. Herein, we report on the clinical features of 13 laboratory-confirmed human cases of B19V-associated encephalitis in Senegal in the framework of a hospital-based surveillance of acute viral encephalitis conducted from 2021 to 2023. Overall, B19V was detected from 13 cerebrospinal fluid samples using specific real time PCR. The mean age was 16.7 years among B19V-positive patients, with a higher prevalence in 0–5-year-old children and the sex ratio (male/female) was 2.25. The B19V-positive patients mainly exhibited hypoleukocytosis, normal glycorrhachia, and normal proteinorrachia in the cerebrospinal fluid. While the main neurological symptoms included meningeal and infectious syndromes. Furthermore, three complete B19V genome sequences were successfully characterized using next-generation sequencing. The newly characterized sequences belonged to the genotype 1a and represent, to date, the first complete B19V genome sequences from Senegal. These sequences could be useful not only in future phylodynamic studies of B19V but also in the development of prevention or treatment countermeasures. Our study is noteworthy for the identification of acute B19V-associated encephalitis in Senegal More investigations on the risk factors associated with B19V transmission in Africa are warranted. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2024)

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11 pages, 578 KiB

Open AccessOpinion

Targeting EBV Episome for Anti-Cancer Therapy: Emerging Strategies and Challenges

by Febri Gunawan Sugiokto and Renfeng Li

Viruses 2025, 17(1), 110; https://doi.org/10.3390/v17010110 - 15 Jan 2025

Viewed by 671

Abstract

As a ubiquitous human pathogen, the Epstein–Barr virus (EBV) has established lifelong persistent infection in about 95% of the adult population. The EBV infection is associated with approximately 200,000 human cancer cases and 140,000 deaths per year. The presence of EBV in tumor [...] Read more.

As a ubiquitous human pathogen, the Epstein–Barr virus (EBV) has established lifelong persistent infection in about 95% of the adult population. The EBV infection is associated with approximately 200,000 human cancer cases and 140,000 deaths per year. The presence of EBV in tumor cells provides a unique advantage in targeting the viral genome (also known as episome), to develop anti-cancer therapeutics. In this review, we summarize current strategies targeting the viral episome in cancer cells. We also highlight emerging technologies, such as clustered regularly interspersed short palindromic repeat (CRISPR)-based gene editing or activation, which offer promising avenues for selective targeting of the EBV episome for anti-cancer therapy. We discuss the challenges, limitations, and future perspectives associated with these strategies, including potential off-target effects, anti-cancer efficacy and safety. Full article

(This article belongs to the Special Issue Epigenetic and Transcriptional Regulation of DNA Virus Infections)

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15 pages, 854 KiB

Open AccessArticle

Interpretation of COVID-19 Epidemiological Trends in Mexico Through Wastewater Surveillance Using Simple Machine Learning Algorithms for Rapid Decision-Making

by Arnoldo Armenta-Castro, Orlando de la Rosa, Alberto Aguayo-Acosta, Mariel Araceli Oyervides-Muñoz, Antonio Flores-Tlacuahuac, Roberto Parra-Saldívar and Juan Eduardo Sosa-Hernández

Viruses 2025, 17(1), 109; https://doi.org/10.3390/v17010109 - 15 Jan 2025

Viewed by 684

Abstract

Detection and quantification of disease-related biomarkers in wastewater samples, denominated Wastewater-based Surveillance (WBS), has proven a valuable strategy for studying the prevalence of infectious diseases within populations in a time- and resource-efficient manner, as wastewater samples are representative of all cases within the [...] Read more.

Detection and quantification of disease-related biomarkers in wastewater samples, denominated Wastewater-based Surveillance (WBS), has proven a valuable strategy for studying the prevalence of infectious diseases within populations in a time- and resource-efficient manner, as wastewater samples are representative of all cases within the catchment area, whether they are clinically reported or not. However, analysis and interpretation of WBS datasets for decision-making during public health emergencies, such as the COVID-19 pandemic, remains an area of opportunity. In this article, a database obtained from wastewater sampling at wastewater treatment plants (WWTPs) and university campuses in Monterrey and Mexico City between 2021 and 2022 was used to train simple clustering- and regression-based risk assessment models to allow for informed prevention and control measures in high-affluence facilities, even if working with low-dimensionality datasets and a limited number of observations. When dividing weekly data points based on whether the seven-day average daily new COVID-19 cases were above a certain threshold, the resulting clustering model could differentiate between weeks with surges in clinical reports and periods between them with an 87.9% accuracy rate. Moreover, the clustering model provided satisfactory forecasts one week (80.4% accuracy) and two weeks (81.8%) into the future. However, the prediction of the weekly average of new daily cases was limited (R² = 0.80, MAPE = 72.6%), likely because of insufficient dimensionality in the database. Overall, while simple, WBS-supported models can provide relevant insights for decision-makers during epidemiological outbreaks, regression algorithms for prediction using low-dimensionality datasets can still be improved. Full article

(This article belongs to the Special Issue Advanced Strategies against SARS-CoV-2 Variants and Future Emerging Virus Outbreaks)

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4 pages, 147 KiB

Open AccessEditorial

Recent Advances of Avian Viruses Research

by Chi-Young Wang

Viruses 2025, 17(1), 99; https://doi.org/10.3390/v17010099 - 14 Jan 2025

Viewed by 555

Abstract

The outbreaks of several epidemics caused by pathogenic avian viruses pose significant threats to the poultry industry [...] Full article

(This article belongs to the Special Issue Recent Advances of Avian Viruses Research)

20 pages, 1056 KiB

Open AccessReview

Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19

by Abigail Vanderheiden and Michael S. Diamond

Viruses 2025, 17(1), 98; https://doi.org/10.3390/v17010098 - 14 Jan 2025

Viewed by 671

Abstract

Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients [...] Read more.

Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, as well as discussing the sequelae that warrant continued and intensive research. Full article

(This article belongs to the Section Coronaviruses)

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9 pages, 1331 KiB

Open AccessArticle

A Survey of Wild Indigenous Cryptostylis ovata Orchid Populations in Western Australia Reveals Spillover of Exotic Viruses

by Stephen Wylie, Hua Li and Shu Hui Koh

Viruses 2025, 17(1), 108; https://doi.org/10.3390/v17010108 - 14 Jan 2025

Viewed by 500

Abstract

Cryptostylis ovata is a terrestrial orchid endemic to southwestern Australia. The virus status of C. ovata has not been studied. Eighty-three C. ovata samples from 16 populations were collected, and sequencing was used to identify RNA viruses from them. In one population, all [...] Read more.

Cryptostylis ovata is a terrestrial orchid endemic to southwestern Australia. The virus status of C. ovata has not been studied. Eighty-three C. ovata samples from 16 populations were collected, and sequencing was used to identify RNA viruses from them. In one population, all tested plants were co-infected with isolates of the exotic-to-Australia viruses Ornithogalum mosaic virus (OrMV) and bean yellow mosaic virus (BYMV). In another population, one plant was infected with BYMV. No viruses were detected in the remaining populations. The OrMV isolate shared 98–99% nucleotide identity with isolates identified from wild indigenous Lachenalia (Iridaceae) plants in South Africa. This suggests that the source of OrMV in C. ovata may be one or more bulbous iridaceous flowering plants of southern African origin that were introduced to Western Australia as ornamentals and that have since become invasive weeds. One BYMV isolate from C. ovata also exhibited 99% nucleotide identity with strains isolated from the exotic leguminous crop Lupinus angustifolius in Western Australia, suggesting possible spillover to indigenous species from this source. This study with C. ovata highlights the probable role of invasive weeds and exotic crops as sources of exotic virus spillovers to indigenous plants. Full article

(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)

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