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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 21625

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Prof. Dr. Carlo Contini

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Infectious Diseases and Dermatology, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
Interests: SARS-CoV-2 and COVID-19; HIV-related opportunistic infections; chlamydia and mycoplasma human infections; cytokines and pathogenesis of infectious diseases; sepsis markers; epidemics of infectious and tropical diseases
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Dear Colleagues,

For many years we have been accustomed to associating certain opportunistic viral infections with HIV/AIDS infection, the pandemic still ongoing around the world that causes thousands of new infections every day and still has a high mortality and lethality rate. AIDS has taught us a great deal about opportunistic infections due to microorganisms that are rare or in themselves often endowed with little virulence, but which multiply to become aggressive pathogens in immunocompromised individuals as a result of infections, therapies or situations leading to immunodepression. Today, however, we must not forget other opportunistic infections that arise in people who do not have HIV/AIDS, but who have frailty because they are affected by non-infectious diseases which require lengthy treatment with anti-tumor, biotechnological and chemotherapeutic drugs in general. Among these, CMV infection, herpesvirus, HBV, and some coronaviruses are just a few examples.

In this Special Issue, we will aim to focus on the most recent advances in opportunistic viral infections from the epidemiological, diagnostic and therapeutic point of view with special regard to the immunocompromised host and the frail and transplanted individual.

Prof. Dr. Carlo Contini
Guest Editor

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Keywords

epidemiology of opportunistic viral infections
immunocompromised individual (HIV/AIDS, transplants, tumors, chemotherapeutics, biotechnologic drugs, etc.)
advances in diagnosis, management and treatment of opportunistic viral infections
HIV
CMV and other herpesvirus
transmissible gastroenteritis virus (TGEV)
human T-Cell leukemia virus type 1 (HTLV-1)
JC virus
HPV
hepatitis B virus (HBV) and hepatitis C virus (HCV)
coronavirus
emerging viruses

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Published Papers (11 papers)

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12 pages, 839 KiB

Open AccessArticle

Risk Factors Associated with Opportunistic Infections among People Living with HIV/AIDS and Receiving an Antiretroviral Therapy in Gabon, Central Africa

by Augustin Mouinga-Ondeme, Neil Michel Longo-Pendy, Ivan Cyr Moussadji Kinga, Barthélémy Ngoubangoye, Pamela Moussavou-Boundzanga, Larson Boundenga, Abdoulaye Diane, Jeanne Sica, Ivan Sosthene Mfouo-Tynga and Edgard Brice Ngoungou

Viruses 2024, 16(1), 85; https://doi.org/10.3390/v16010085 - 4 Jan 2024

Viewed by 1945

Abstract

The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the main causes of death in sub-Saharan Africa. Antiretroviral therapies (ARTs) have significantly improved the health conditions of people living with HIV/AIDS (PLWHA). Consequently, a significant drop in morbidity and mortality, along with a reduced incidence of opportunistic infections (OIs), has been observed. However, certain atypical and biological profiles emerge in ART patients post-examination. The objective of this study was to identify the risk factors that contributed to the onset of OIs in HIV patients undergoing ART in Gabon. Epidemiological and biological data were obtained from medical records (2017 to 2019) found at the outpatient treatment centre (CTA) of Franceville in Gabon. Samples for blood count, CD4, and viral load analysis at CIRMF were collected from PLWHA suffering from other pathogen-induced conditions. A survey was carried out and data were analysed using Rstudio 4.0.2 and Excel 2007 software. Biological and socio-demographic characteristics were examined concerning OIs through both a univariate analysis via Fisher’s exact tests or chi² (χ²), and a multivariate analysis via logistic regression. Out of the 300 participants initially selected, 223 were included in the study, including 154 (69.05%) women and 69 (30.95%) men. The mean age was 40 (38.6; 41.85), with individuals ranging from 2 to 77 years old. The study cohort was classified into five age groups (2 to 12, 20 to 29, 30 to 39, 40 to 49, and 50 to 77 years old), among which the groups aged 30 to 39 and 40 to 49 emerged as the largest, comprising 68 (30.5%) and 75 (33.6%) participants, respectively. It was noted that 57.9% of PLWHA had developed OIs and three subgroups were distinguished, with parasitic, viral, and bacterial infections present in 18%, 39.7%, and 55.4% of cases, respectively. There was a correlation between being male and having a low CD4 T-cell count and the onset of OIs. The study revealed a high overall prevalence of OIs, and extending the study to other regions of Gabon would yield a better understanding of the risk factors associated with the onset of these infections. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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14 pages, 1687 KiB

Open AccessArticle

Investigating the Role of Anti-TPO Antibodies in HIV-Associated Thrombocytopenia before and after Initiation of HAART: A Case-Control Longitudinal Study

by Aristotelis Tsiakalos, John G. Routsias, Georgios Schinas, Sarah Georgiadou, Nikolaos V. Sipsas and Karolina Akinosoglou

Viruses 2023, 15(11), 2226; https://doi.org/10.3390/v15112226 - 8 Nov 2023

Viewed by 1390

Abstract

This longitudinal, case-control study aimed to investigate the role of thrombopoietin (TPO) and anti-TPO antibodies in HIV-associated thrombocytopenia, focusing on the changes seen before and after the initiation of highly active antiretroviral therapy (HAART). Patients were assessed before and at least six months after the initiation of HAART. In total, 75 PLWHIV (age/sex-matched and randomized at 2:1, according to thrombocytopenia status) were included in this study. The baseline assessment revealed significantly higher TPO levels in thrombocytopenic patients (140.45 vs. 106.8 mg/mL, p = 0.008). Furthermore, anti-TPO-positive patients displayed lower platelet counts (109,000 vs. 139,000/L, p = 0.002) and TPO levels (114.7 vs. 142.7 mg/mL, p = 0.047). Longitudinally, HAART initiation reduced the frequency of thrombocytopenia from 75.47% to 33.96% (p < 0.001) and elevated the median platelet counts from 131,000 to 199,000 (p < 0.001). No significant difference in median platelet counts was found post-HAART among the anti-TPO subgroups (p = 0.338), a result contrasting with pre-HAART findings (p = 0.043). Changes in anti-TPO status corresponded with significant platelet count alterations (p = 0.036). Notably, patients who became anti-TPO negative showed a median increase of 95,000 platelets (IQR: 43,750–199,500). These marked differences between subgroups underscore the potential role of anti-TPO antibodies in modulating the hematological response to HAART. Further research is needed to elucidate the complex interplay between HIV infection, HAART, and thrombocytopenia. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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15 pages, 3250 KiB

Open AccessArticle

Patterns of Circulating Cytokines and Vascular Markers’ Response in the Presence of COVID-19 in Kidney Transplant Recipients Compared with Non-Transplanted Patients

by Milena Karina Coló Brunialti, Giuseppe G. F. Leite, Gabriela Strafolino Eburneo, Orlei Ribeiro de Araujo, Paula M. Peçanha-Pietrobom, Paulo Roberto Abrão Ferreira, Nancy C. Junqueira Bellei, Jaquelina Sonoe Ota Arakaki, José Medina-Pestana, Lúcio Requião-Moura and Reinaldo Salomao

Viruses 2023, 15(11), 2166; https://doi.org/10.3390/v15112166 - 28 Oct 2023

Viewed by 1144

Abstract

COVID-19’s severity has been associated with a possible imbalance in the cross-regulation of cytokines and vascular mediators. Since the beginning of the pandemic, kidney transplant recipients (KTRs) have been identified as patients of high vulnerability to more severe diseases. Thus, aiming to describe the patterns of cytokines and vascular mediators and to trace patients’ differences according to their KTR status, this prospective study enrolled 67 COVID-19 patients (20 KTRs) and 29 non-COVID-19 controls before vaccination. A panel comprising 17 circulating cytokines and vascular mediators was run on samples collected at different time points. The cytokine and mediator patterns were investigated via principal component analysis (PCA) and correlation-based network (CBN). In both groups, compared to their respective controls, COVID-19 was associated with higher levels of cytokines and vascular mediators. Differentiating between the KTRs and non-KTRs, the number of correlations was much higher in the non-KTRs (44 vs. 14), and the node analysis showed the highest interactions of NGAL and sVCAM-1 in the non-KTRs and KTRs (9 vs. 4), respectively. In the PCA, while the non-KTRs with COVID-19 were differentiated from their controls in their IL-10, IFN-α, and TNF-α, this pattern was marked in the NGAL, sVCAM-1, and IL-8 of the KTRs. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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13 pages, 1841 KiB

Open AccessArticle

Characteristics of Anti-Measles Immunity in Lung Transplant Candidates

by Valentina B. Polishchuk, Mikhail P. Kostinov, Aleksey A. Ryzhov, Natalia A. Karchevskaya, Irina L. Solov’eva, Alexander P. Cherdantsev, Aristitsa M. Kostinova and Arseniy A. Poddubikov

Viruses 2023, 15(10), 2121; https://doi.org/10.3390/v15102121 - 19 Oct 2023

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Abstract

Measles has not yet been eradicated; therefore, its outbreaks are still reported throughout the world. Like any infection, measles is dangerous for immunocompromised patients. Levels of anti-measles IgG antibodies were measured in 157 patients aged 17 to 72, who were placed on the lung transplant waiting list. Measurements were undertaken by enzyme-linked immunosorbent assay (ELISA) using the VectoMeasles-IgG kit (Russia). The proportion of patients seronegative for measles was 19% (30/157). Correlation was detected between patients’ age and their levels of anti-measles antibodies, with higher proportions of patients having undetectable titers (25.5–28.9%) or low antibody levels (38.3–44.4%) in the young age groups (17–29 and 30–39 years old). There were no differences between male and female patients in levels of anti-measles antibodies or in the proportion of seronegative individuals. Analyses of antibody levels with regard to type of disease revealed the highest rate of seronegative results in cystic fibrosis patients (34.4%, 11/32). Overall, 19% of lung transplant candidates, mostly young people and cystic fibrosis patients, did not have protective immunity against measles. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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14 pages, 3877 KiB

Open AccessCommunication

Burden of HPV-Related Hospitalization in Germany from 2000 to 2021

by Georgios Tampakoudis and Olympia E. Anastasiou

Viruses 2023, 15(9), 1857; https://doi.org/10.3390/v15091857 - 31 Aug 2023

Cited by 1 | Viewed by 1774

Abstract

HPV has been linked to the development of precancerous and cancerous lesions. The aim of this study was to evaluate the burden of HPV-related hospitalization in Germany from 2000 to 2021 and the potential impact of the COVID-19 pandemic on it. Methods: We performed a retrospective query using data from the German Statistical Office from 2000 to 2021, including hospital admission, inpatient mortality and hospital stay length data on cervical cancer/dysplasia, female genitourinary tract, anal, penile, head and neck cancers. Results: The HPV-attributable hospitalization rate per 100,000 inhabitants in Germany has decreased over time, from 89 cases in 2000 to 60 in 2021, with an average annual percent change (AAPC) of −1.93 (CI −2.08–−1.79, p < 0.05). The same trend was observed for the average hospital stay, which declined from 9 to 7 days, with an AAPC of −1.33 (CI −1.52–−1.21, p < 0.05). An undulating but overall slightly declining pattern was observed for the inpatient mortality (AAPC −0.92, CI −1.21–−0.64, p < 0.05). We observed a reduction in the hospitalization rates for invasive and non-invasive cervical cancer, which was observed in almost all age groups and in all German federal states. Conclusion: Our study provides a comprehensive analysis of the trends in HPV-related hospitalizations over the past two decades. The decline in hospitalization rates for cervical cancer and dysplasia suggests the potential efficacy of the HPV vaccination and screening programs. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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13 pages, 956 KiB

Open AccessArticle

Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients

by Martina Gambato, Chiara Manuli, Erica N. Lynch, Sara Battistella, Giacomo Germani, Marco Senzolo, Alberto Zanetto, Alberto Ferrarese, Alessandro Vitale, Enrico Gringeri, Umberto Cillo, Patrizia Burra and Francesco Paolo Russo

Viruses 2023, 15(8), 1702; https://doi.org/10.3390/v15081702 - 7 Aug 2023

Cited by 1 | Viewed by 1645

Abstract

(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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21 pages, 2509 KiB

Open AccessArticle

Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011–2020

by Kazuo Nakamichi, Yoshiharu Miura, Toshio Shimokawa, Kenta Takahashi, Tadaki Suzuki, Nobuaki Funata, Masafumi Harada, Koichiro Mori, Nobuo Sanjo, Motohiro Yukitake, Kazuya Takahashi, Tsuyoshi Hamaguchi, Shoko Izaki, Satoru Oji, Jin Nakahara, Ryusuke Ae, Koki Kosami, Souichi Nukuzuma, Yosikazu Nakamura, Kyoichi Nomura, Shuji Kishida, Hidehiro Mizusawa, Masahito Yamada, Masaki Takao, Hideki Ebihara and Masayuki Saijo Show full author list Hide full author list

Viruses 2023, 15(4), 968; https://doi.org/10.3390/v15040968 - 14 Apr 2023

Cited by 8 | Viewed by 2740

Abstract

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011–2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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10 pages, 1183 KiB

Open AccessCommunication

Molecular Screening for High-Risk Human Papillomaviruses in Patients with Periodontitis

by Kalina Shishkova, Raina Gergova, Elena Tasheva, Stoyan Shishkov and Ivo Sirakov

Viruses 2023, 15(3), 809; https://doi.org/10.3390/v15030809 - 22 Mar 2023

Cited by 3 | Viewed by 1767

Abstract

Members of the Papillomaviridae family account for 27.9–30% of all infectious agents associated with human cancer. The aim of our study was to investigate the presence of high-risk HPV (human papilloma virus) genotypes in patients with periodontitis and a pronounced clinical picture. To achieve this goal, after proving the bacterial etiology of periodontitis, the samples positive for bacteria were examined for the presence of HPV. The genotype of HPV is also determined in samples with the presence of the virus proven by PCR (polymerase chain reaction). All positive tests for bacteria associated with the development of periodontitis indicated the presence of HPV. There was a statistically significant difference in HPV positive results between the periodontitis positive target group and the control group. The higher presence of high-risk HPV genotypes in the target group, which was also positive for the presence of periodontitis-causing bacteria, has been proven. A statistically significant relationship was established between the presence of periodontitis-causing bacteria and high-risk strains of HPV. The most common HPV genotype that tests positive for bacteria associated with the development of periodontitis is HPV58. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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Review

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23 pages, 1725 KiB

Open AccessReview

Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

by Maria Antonia De Francesco

Viruses 2024, 16(1), 133; https://doi.org/10.3390/v16010133 - 17 Jan 2024

Cited by 5 | Viewed by 3326

Abstract

Alzheimer’s disease and Parkinson’s disease represent the most common forms of cognitive impairment. Multiple sclerosis is a chronic inflammatory disease of the central nervous system responsible for severe disability. An aberrant immune response is the cause of myelin destruction that covers axons in the brain, spinal cord, and optic nerves. Systemic lupus erythematosus is an autoimmune disease characterized by alteration of B cell activation, while Sjögren’s syndrome is a heterogeneous autoimmune disease characterized by altered immune responses. The etiology of all these diseases is very complex, including an interrelationship between genetic factors, principally immune associated genes, and environmental factors such as infectious agents. However, neurodegenerative and autoimmune diseases share proinflammatory signatures and a perturbation of adaptive immunity that might be influenced by herpesviruses. Therefore, they might play a critical role in the disease pathogenesis. The aim of this review was to summarize the principal findings that link herpesviruses to both neurodegenerative and autoimmune diseases; moreover, briefly underlining the potential therapeutic approach of virus vaccination and antivirals. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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Other

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12 pages, 1161 KiB

Open AccessBrief Report

COVID-19 Disease in Pediatric Solid Organ Transplantation from Alpha to Omicron: A High Monocyte Count in the Preceding Three Months Portends a Risk for Severe Disease

by Yasmina Sirgi, Maja Stanojevic, Jaeil Ahn, Nada Yazigi, Stuart Kaufman, Khalid Khan, Bernadette Vitola, Cal Matsumoto, Alexander Kroemer, Thomas Fishbein and Udeme D. Ekong

Viruses 2023, 15(7), 1559; https://doi.org/10.3390/v15071559 - 16 Jul 2023

Cited by 1 | Viewed by 1543

Abstract

Importance: Planning for future resurgences in SARS-CoV-2 infection is necessary for providers who care for immunocompromised patients. Objective: to determine factors associated with COVID-19 disease severity in immunosuppressed children. Design: a case series of children with solid organ transplants diagnosed with SARS-CoV-2 infection between 15 March 2020 and 31 March 2023. Setting: a single pediatric transplant center. Participants: all children with a composite transplant (liver, pancreas, intestine), isolated intestine transplant (IT), isolated liver transplant LT), or simultaneous liver kidney transplant (SLK) with a positive PCR for SARS-CoV-2. Exposure: SARS-CoV-2 infection. Main outcome and measures: We hypothesized that children on the most immunosuppression, defined by the number of immunosuppressive medications and usage of steroids, would have the most severe disease course and that differential white blood cell count in the months preceding infection would be associated with likelihood of having severe disease. The hypothesis being tested was formulated during data collection. The primary study outcome measurement was disease severity defined using WHO criteria. Results: 77 children (50 LT, 24 intestine, 3 SLK) were infected with SARS-CoV-2, 57.4 months from transplant (IQR 19.7–87.2). 17% were ≤1 year post transplant at infection. 55% were male, 58% were symptomatic and ~29% had severe disease. A high absolute lymphocyte count at diagnosis decreased the odds of having severe COVID-19 disease (OR 0.29; CI 0.11–0.60; p = 0.004). Conversely, patients with a high absolute monocyte count in the three months preceding infection had increased odds of having severe disease (OR 30.49; CI 1.68–1027.77; p = 0.033). Steroid use, higher tacrolimus level, and number of immunosuppressive medications at infection did not increase the odds of having severe disease. Conclusions and relevance: The significance of a high monocyte count as predictor of severe disease potentially confirms the importance of monocytic inflammasome-driven inflammation in COVID-19 pathogenesis. Our data do not support reducing immunosuppression in the setting of infection. Our observations may have important ramifications in resource management as vaccine- and infection-induced immunity wanes. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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8 pages, 3662 KiB

Open AccessBrief Report

Role of Histamine and Related Signaling in Kaposi’s Sarcoma-Associated Herpesvirus Pathogenesis and Oncogenesis

by Jungang Chen, Jiao Song, Karlie Plaisance-Bonstaff, Shengyu Mu, Steven R. Post, Lu Dai and Zhiqiang Qin

Viruses 2023, 15(4), 1011; https://doi.org/10.3390/v15041011 - 20 Apr 2023

Viewed by 1830

Abstract

Although Kaposi’s sarcoma-associated herpesvirus (KSHV) has been reported to cause several human cancers including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), the mechanisms of KSHV-induced tumorigenesis, especially virus–host interaction network, are still not completely understood, which therefore hinders the development of effective therapies. Histamine, together with its receptors, plays an important role in various allergic diseases by regulating different inflammation and immune responses. Our previous data showed that antagonists targeting histamine receptors effectively repressed KSHV lytic replication. In the current study, we determined that histamine treatment increased cell proliferation and anchorage-independent growth abilities of KSHV-infected cells. Furthermore, histamine treatment affected the expression of some inflammatory factors from KSHV-infected cells. For clinical relevance, several histamine receptors were highly expressed in AIDS-KS tissues when compared to normal skin tissues. We determined that histamine treatment promoted KSHV-infected lymphoma progression in immunocompromised mice models. Therefore, besides viral replication, our data indicate that the histamine and related signaling are also involved in other functions of KSHV pathogenesis and oncogenesis. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections)

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