Viruses

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Open AccessArticle

In Vitro Evaluation of the Antiviral Activity of the Synthetic Epigallocatechin Gallate Analog-Epigallocatechin Gallate (EGCG) Palmitate against Porcine Reproductive and Respiratory Syndrome Virus

by Chunjian Zhao, Shuaihua Liu, Chunying Li, Lei Yang and Yuangang Zu

Viruses 2014, 6(2), 938-950; https://doi.org/10.3390/v6020938 - 21 Feb 2014

Cited by 33 | Viewed by 7263

Abstract

In this study, epigallocatechin gallate (EGCG) palmitate was synthesized and its anti-porcine reproductive and respiratory syndrome virus (PRRSV) activity was studied. Specifically, EGCG palmitate was evaluated for its ability to inhibit PRRSV infection in MARC-145 cells when administered as pre-, post-, or co-treatment. [...] Read more.

In this study, epigallocatechin gallate (EGCG) palmitate was synthesized and its anti-porcine reproductive and respiratory syndrome virus (PRRSV) activity was studied. Specifically, EGCG palmitate was evaluated for its ability to inhibit PRRSV infection in MARC-145 cells when administered as pre-, post-, or co-treatment. EGCG and ribavirin were used as controls. The results showed that a 50% cytotoxic concentration (CC50) of EGCG, EGCG palmitate, and ribavirin was achieved at 2,359.71, 431.42, and 94.06 μM, respectively. All three drugs inhibited PRRSV in a dose-dependent manner regardless of the treatment protocol. EGCG palmitate exhibited higher cytotoxicity than EGCG, but lower cytotoxicity than ribavirin. EGCG palmitate anti-PRRSV activity was significantly higher than that of EGCG and ribavirin, both as pre-treatment and post-treatment. Under the former conditions and a tissue culture infectious dose of 10 and 100, the selectivity index (SI) of EGCG palmitate in the inhibition of PRRSV was 3.8 and 2.9 times higher than that of ribavirin when administered as a pre-treatment, while the SI of EGCG palmitate in the inhibition of PRRSV was 3.0 and 1.9 times higher than ribavirin when administered as a post-treatment. Therefore, EGCG palmitate is potentially effective as an anti-PRRSV agent and thus of interest to the pharmaceutical industry. Full article

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

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Open AccessArticle

Clinical Documentation and Data Transfer from Ebola and Marburg Virus Disease Wards in Outbreak Settings: Health Care Workers’ Experiences and Preferences

by Silja Bühler, Paul Roddy, Ellen Nolte and Matthias Borchert

Viruses 2014, 6(2), 927-937; https://doi.org/10.3390/v6020927 - 19 Feb 2014

Cited by 13 | Viewed by 12416

Abstract

Understanding human filovirus hemorrhagic fever (FHF) clinical manifestations and evaluating treatment strategies require the collection of clinical data in outbreak settings, where clinical documentation has been limited. Currently, no consensus among filovirus outbreak-response organisations guides best practice for clinical documentation and data transfer. [...] Read more.

Understanding human filovirus hemorrhagic fever (FHF) clinical manifestations and evaluating treatment strategies require the collection of clinical data in outbreak settings, where clinical documentation has been limited. Currently, no consensus among filovirus outbreak-response organisations guides best practice for clinical documentation and data transfer. Semi-structured interviews were conducted with health care workers (HCWs) involved in FHF outbreaks in sub-Saharan Africa, and with HCWs experienced in documenting and transferring data from high-risk areas (isolation wards or biosafety level 4 laboratories). Methods for data documentation and transfer were identified, described in detail and categorised by requirement for electricity and ranked by interviewee preference. Some methods involve removing paperwork and other objects from the filovirus disease ward without disinfection. We believe that if done properly, these methods are reasonably safe for certain settings. However, alternative methods avoiding the removal of objects, or involving the removal of paperwork or objects after non-damaging disinfection, are available. These methods are not only safer, they are also perceived as safer and likely more acceptable to health workers and members of the community. The use of standardised clinical forms is overdue. Experiments with by sunlight disinfection should continue, and non-damaging disinfection of impregnated paper, suitable tablet computers and underwater cameras should be evaluated under field conditions. Full article

(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)

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Open AccessReview

Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

by Dawn L. Weir, Edward J. Annand, Peter A. Reid and Christopher C. Broder

Viruses 2014, 6(2), 909-926; https://doi.org/10.3390/v6020909 - 19 Feb 2014

Cited by 20 | Viewed by 12573

Abstract

Australian bat lyssavirus (ABLV) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats [...] Read more.

Australian bat lyssavirus (ABLV) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats (genus Pteropus) and the other in insectivorous microbats (genus Saccolaimus). Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incubation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G). Recent studies have revealed that proposed rabies virus (RABV) receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

The Tetraspanin CD151 in Papillomavirus Infection

by Konstanze D. Scheffer, Fedor Berditchevski and Luise Florin

Viruses 2014, 6(2), 893-908; https://doi.org/10.3390/v6020893 - 18 Feb 2014

Cited by 40 | Viewed by 11266

Abstract

Human papillomaviruses (HPV) are non-enveloped DNA tumor viruses that infect skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers. During the multistep process of infection, numerous host proteins are required for [...] Read more.

Human papillomaviruses (HPV) are non-enveloped DNA tumor viruses that infect skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers. During the multistep process of infection, numerous host proteins are required for the delivery of virus genetic information into the nucleus of target cells. Over the last two decades, many host-cell proteins such as heparan sulfate proteoglycans, integrins, growth factor receptors, actin and the tetraspanin CD151 have been described to be involved in the process of infectious entry of HPV16. Tetraspanins have the ability to organize membrane microdomains and to directly influence the function of associated molecules, including binding of receptors to their ligands, receptor oligomerization and signal transduction. Here, we summarize the current knowledge on CD151, and CD151-associated partners during HPV infection and discuss the underlying mechanisms. Full article

(This article belongs to the Special Issue Viruses and Tetraspanins)

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Open AccessReview

CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

by Laetitia Zona, Rajiv G. Tawar, Mirjam B. Zeisel, Fei Xiao, Catherine Schuster, Joachim Lupberger and Thomas F. Baumert

Viruses 2014, 6(2), 875-892; https://doi.org/10.3390/v6020875 - 18 Feb 2014

Cited by 30 | Viewed by 11613

Abstract

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into [...] Read more.

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection. Full article

(This article belongs to the Special Issue Viruses and Tetraspanins)

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Open AccessArticle

Anti-Tumor Effects of an Oncolytic Adenovirus Expressing Hemagglutinin-Neuraminidase of Newcastle Disease Virus in Vitro and in Vivo

by Dongyun He, Lili Sun, Chang Li, Ningning Hu, Yuan Sheng, Zhifei Chen, Xiao Li, Baorong Chi and Ningyi Jin

Viruses 2014, 6(2), 856-874; https://doi.org/10.3390/v6020856 - 18 Feb 2014

Cited by 17 | Viewed by 7590

Abstract

Oncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. [...] Read more.

Oncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. Here, we assessed the ability of a novel dual-specific anti-tumor oncolytic adenovirus, expressing the hemagglutinin-neuraminidase (HN) gene from the Newcastle disease virus under the human telomerase reverse transcriptase (hTERT) promoter (Ad-hTERTp-E1a-HN), to inhibit esophageal cancer EC-109 cells in culture and to reduce tumor burden in xenografted BALB/c nude mice. In vitro, infection with Ad-hTERT-E1a-HN could inhibit the growth of EC-109 cells significantly and also protect normal human liver cell line L02 from growth suppression in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Ad-hTERT-E1a-HN also effectively and selectively decreased the sialic acid level on EC-109 cells, but not on L02 cells. Furthermore, Ad-hTERT-E1a-HN was shown to induce the apoptosis pathway via acridine orange and ethidium bromide staining (AO/EB staining), increase reactive oxygen species (ROS), reduce mitochondrial membrane potential and release cytochrome c. In vivo, xenografted BALB/c nude mice were treated via intratumoral or intravenous injections of Ad-hTERT-E1a-HN. Although both treatments showed an obvious suppression in tumor volume, only Ad-hTERT-E1a-HN delivered via intratumoral injection elicited a complete response to treatment. These results reinforced previous findings and highlighted the potential therapeutic application of Ad-hTERT-E1a-HN for treatment of esophageal cancer in clinical trials. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

The Evolution of Adenoviral Vectors through Genetic and Chemical Surface Modifications

by Cristian Capasso, Mariangela Garofalo, Mari Hirvinen and Vincenzo Cerullo

Viruses 2014, 6(2), 832-855; https://doi.org/10.3390/v6020832 - 17 Feb 2014

Cited by 47 | Viewed by 11229

Abstract

A long time has passed since the first clinical trial with adenoviral (Ad) vectors. Despite being very promising, Ad vectors soon revealed their limitations in human clinical trials. The pre-existing immunity, the marked liver tropism and the high toxicity of first generation Ad [...] Read more.

A long time has passed since the first clinical trial with adenoviral (Ad) vectors. Despite being very promising, Ad vectors soon revealed their limitations in human clinical trials. The pre-existing immunity, the marked liver tropism and the high toxicity of first generation Ad (FG-Ad) vectors have been the main challenges for the development of new approaches. Significant effort toward the development of genetically and chemically modified adenoviral vectors has enabled researchers to create more sophisticated vectors for gene therapy, with an improved safety profile and a higher transduction ability of different tissues. In this review, we will describe the latest findings in the high-speed, evolving field of genetic and chemical modifications of adenoviral vectors, a field in which different disciplines, such as biomaterial research, virology and immunology, co-operate synergistically to create better gene therapy tools for modern challenges. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

by Annette Fink, Julia K. Büttner, Doris Thomas, Rafaela Holtappels, Matthias J. Reddehase and Niels A. W. Lemmermann

Viruses 2014, 6(2), 808-831; https://doi.org/10.3390/v6020808 - 14 Feb 2014

Cited by 7 | Viewed by 7398

Abstract

Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. [...] Read more.

Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs) based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 D^d and that is immunodominant in BALB/c (H-2^d haplotype) mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E) phase protein, the m164 epitope is presented already during the Immediate Early (IE) phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessReview

HCMV Reprogramming of Infected Monocyte Survival and Differentiation: A Goldilocks Phenomenon

by Emily V. Stevenson, Donna Collins-McMillen, Jung Heon Kim, Stephen J. Cieply, Gretchen L. Bentz and Andrew D. Yurochko

Viruses 2014, 6(2), 782-807; https://doi.org/10.3390/v6020782 - 13 Feb 2014

Cited by 64 | Viewed by 8916

Abstract

The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV) infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes [...] Read more.

The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV) infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes are also known to play a key role in viral latency and life-long persistence. However, in order to utilize infected monocytes for viral spread and persistence, HCMV must overcome a number of monocyte biological hurdles, including their naturally short lifespan and their inability to support viral gene expression and replication. Our laboratory has shown that HCMV is able to manipulate the biology of infected monocytes in order to overcome these biological hurdles by inducing the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral gene expression and replication. In this current review, we describe the unique aspects of how HCMV promotes monocyte survival and differentiation by inducing a “finely-tuned” macrophage cell type following infection. Specifically, we describe the induction of a uniquely polarized macrophage subset from infected monocytes, which we argue is the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessReview

Experimental Infections of Wild Birds with West Nile Virus

by Elisa Pérez-Ramírez, Francisco Llorente and Miguel Ángel Jiménez-Clavero

Viruses 2014, 6(2), 752-781; https://doi.org/10.3390/v6020752 - 13 Feb 2014

Cited by 125 | Viewed by 13004

Abstract

Avian models of West Nile virus (WNV) disease have become pivotal in the study of infection pathogenesis and transmission, despite the intrinsic constraints that represents this type of experimental research that needs to be conducted in biosecurity level 3 (BSL3) facilities. This review [...] Read more.

Avian models of West Nile virus (WNV) disease have become pivotal in the study of infection pathogenesis and transmission, despite the intrinsic constraints that represents this type of experimental research that needs to be conducted in biosecurity level 3 (BSL3) facilities. This review summarizes the main achievements of WNV experimental research carried out in wild birds, highlighting advantages and limitations of this model. Viral and host factors that determine the infection outcome are analyzed in detail, as well as recent discoveries about avian immunity, viral transmission, and persistence achieved through experimental research. Studies of laboratory infections in the natural host will help to understand variations in susceptibility and reservoir competence among bird species, as well as in the epidemiological patterns found in different affected areas. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV) Pentameric Complex Proteins GP129, 131 and 133

by Josephine S. Gnanandarajah, Peter A. Gillis, Nelmary Hernandez-Alvarado, LeeAnn Higgins, Todd W. Markowski, Heungsup Sung, Sheila Lumley and Mark R. Schleiss

Viruses 2014, 6(2), 727-751; https://doi.org/10.3390/v6020727 - 13 Feb 2014

Cited by 12 | Viewed by 7205

Abstract

Development of a vaccine against congenital infection with human cytomegalovirus (HCMV) is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC) of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some [...] Read more.

Development of a vaccine against congenital infection with human cytomegalovirus (HCMV) is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC) of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV), consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessArticle

Quantifying Susceptibility of CD4⁺ Stem Memory T-Cells to Infection by Laboratory Adapted and Clinical HIV-1 Strains

by Jacqueline K. Flynn, Geza Paukovics, Kieran Cashin, Katharina Borm, Anne Ellett, Michael Roche, Martin R. Jakobsen, Melissa J. Churchill and Paul R. Gorry

Viruses 2014, 6(2), 709-726; https://doi.org/10.3390/v6020709 - 10 Feb 2014

Cited by 26 | Viewed by 8702

Abstract

CD4⁺ T cells are principal targets for human immunodeficiency virus type 1 (HIV-1) infection. CD4⁺ T cell subsets are heterogeneous cell populations, divided by functional and phenotypic differences into naïve and memory T cells. The memory CD4⁺ T cells are [...] Read more.

CD4⁺ T cells are principal targets for human immunodeficiency virus type 1 (HIV-1) infection. CD4⁺ T cell subsets are heterogeneous cell populations, divided by functional and phenotypic differences into naïve and memory T cells. The memory CD4⁺ T cells are further segregated into central, effector and transitional memory cell subsets by functional, phenotypic and homeostatic characteristics. Defining the distribution of HIV-1 infection in different T cell subsets is important, as this can play a role in determining the size and composition of the viral reservoir. Both central memory and transitional memory CD4⁺ T cells have been described as long-lived viral reservoirs for HIV. Recently, the newly described stem memory T cell subset has also been implicated as a long-lived HIV reservoir. Using green fluorescent protein (GFP) reporter strains of HIV-1 and multi parameter flow cytometry, we developed an assay to simultaneously quantify the susceptibility of stem memory (TSCM), central memory, effector memory, transitional memory and naïve CD4⁺ T cell subsets, to HIV-1 infection in vitro. We show that TSCM are susceptible to infection with laboratory adapted and clinical HIV-1 strains. Our system facilitates the quantitation of HIV-1 infection in alternative T cell subsets by CCR5- and CXCR4-using viruses across different HIV-1 subtypes, and will be useful for studies of HIV-1 pathogenesis and viral reservoirs. Full article

(This article belongs to the Special Issue HIV Latency)

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Open AccessReview

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

by Manoj N. Krishnan and Mariano A. Garcia-Blanco

Viruses 2014, 6(2), 683-708; https://doi.org/10.3390/v6020683 - 10 Feb 2014

Cited by 61 | Viewed by 9238

Abstract

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due [...] Read more.

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. Full article

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

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Open AccessArticle

Intracellular Trafficking of the Human Cytomegalovirus-Encoded 7-trans-Membrane Protein Homologs pUS27 and pUL78 during Viral Infection: A Comparative Analysis

by Ina Niemann, Anna Reichel and Thomas Stamminger

Viruses 2014, 6(2), 661-682; https://doi.org/10.3390/v6020661 - 10 Feb 2014

Cited by 8 | Viewed by 8803

Abstract

Human cytomegalovirus (HCMV) encodes four G protein-coupled receptor (GPCR) homologs, termed pUS27, pUS28, pUL33, and pUL78. In contrast to the extensively characterized vGPCRs pUS28 and pUL33, knowledge concerning pUS27 and pUL78 is limited. Previous studies already demonstrated constitutive internalization of pUS27 and pUL78, [...] Read more.

Human cytomegalovirus (HCMV) encodes four G protein-coupled receptor (GPCR) homologs, termed pUS27, pUS28, pUL33, and pUL78. In contrast to the extensively characterized vGPCRs pUS28 and pUL33, knowledge concerning pUS27 and pUL78 is limited. Previous studies already demonstrated constitutive internalization of pUS27 and pUL78, as well as an association with the endosomal machinery, however, these results were mainly obtained using transiently transfected cells. To explore the subcellular localization of both receptors during viral infection, we constructed recombinant HCMVs expressing tagged vGPCRs. Colocalization analyses revealed a predominant association of pUS27 or pUL78 with the trans-Golgi network or the endoplasmic reticulum, respectively. Intriguingly, our data emphasize that protein sorting is highly regulated by viral functions as we detected dramatic changes in the colocalization of pUS27 and pUL78 with endosomal markers during progression of HCMV replication. Furthermore, we observed cell type-dependent differences in trafficking of both vGPCRs between fibroblasts and epithelial cells. Most importantly, infection experiments with a recombinant HCMV carrying tagged versions of pUS27 and pUL78 simultaneously, revealed that these two proteins do not colocalize during viral infection. This contrasts to results of transient expression experiments. In conclusion, our results highlight the importance to investigate vGPCR trafficking in a viral context. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessArticle

The Use of Chimeric Virus-like Particles Harbouring a Segment of Hantavirus Gc Glycoprotein to Generate a Broadly-Reactive Hantavirus-Specific Monoclonal Antibody

by Aurelija Zvirbliene, Indre Kucinskaite-Kodze, Ausra Razanskiene, Rasa Petraityte-Burneikiene, Boris Klempa, Rainer G. Ulrich and Alma Gedvilaite

Viruses 2014, 6(2), 640-660; https://doi.org/10.3390/v6020640 - 7 Feb 2014

Cited by 10 | Viewed by 8703

Abstract

Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian [...] Read more.

Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. To generate MAbs against hantavirus glycoprotein Gc, we have used initially a recombinant yeast-expressed full-length Puumala virus (PUUV) Gc protein. However, this approach was unsuccessful. As an alternative recombinant antigen, chimeric virus-like particles (VLPs) harboring a segment of PUUV Gc glycoprotein were generated in yeast Saccharomyces cerevisiae. A 99 amino acid (aa)-long segment of Gc protein was inserted into the major capsid protein VP1 of hamster polyomavirus at previously defined positions: either site #1 (aa 80–89) or site #4 (aa 280–289). The chimeric proteins were found to self-assemble to VLPs as evidenced by electron microscopy. Chimeric VLPs induced an efficient insert-specific antibody response in immunized mice. Monoclonal antibody (clone #10B8) of IgG isotype specific to hantavirus Gc glycoprotein was generated. It recognized recombinant full-length PUUV Gc glycoprotein both in ELISA and Western blot assay and reacted specifically with hantavirus-infected cells in immunofluorescence assay. Epitope mapping studies revealed the N-terminally located epitope highly conserved among different hantavirus strains. In conclusion, our approach to use chimeric VLPs was proven useful for the generation of virus-reactive MAb against hantavirus Gc glycoprotein. The generated broadly-reactive MAb #10B8 might be useful for various diagnostic applications. Full article

(This article belongs to the Special Issue Hantaviruses)

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Open AccessArticle

Respiratory Syncytial Virus Persistence in Macrophages Upregulates Fcgamma Receptors Expression

by Jorge Gaona, Carlos Santiago-Olivares, Enrique Ortega and Beatriz Gómez

Viruses 2014, 6(2), 624-639; https://doi.org/10.3390/v6020624 - 6 Feb 2014

Cited by 13 | Viewed by 6632

Abstract

Viruses can persist in differentiated cells (i.e., macrophages) over long periods of time, altering host cells functions but not inducing their death. We had previously reported that, in early passages (14–40) of a murine macrophage-like cell line persistently infected with respiratory [...] Read more.

Viruses can persist in differentiated cells (i.e., macrophages) over long periods of time, altering host cells functions but not inducing their death. We had previously reported that, in early passages (14–40) of a murine macrophage-like cell line persistently infected with respiratory syncytial virus (RSV) (MfP), FcgR-mediated phagocytosis and expression of FcgRIIB/RIII on the cell membrane were increased with respect to mock-infected macrophages (MfN). In this work, we explored the mechanism underlying such effects. Increases in FcgR expression and FcgR-mediated phagocytosis are preserved after more than 87 passages of the persistently infected culture. We analyzed the expression of FcgR isoforms at both mRNA and protein levels, and found out that RSV persistence distinctly affects the expression of FcgR isoforms. We also observed that the increase in FcgRs expression results neither from soluble factors (cytokines) or viral products released by the infected cells, nor from an increase in the rate of FcgR internalization. Our results suggest that RSV persistence in macrophages induce intracellular effects that have an impact on FcgRs gene expression at both mRNA and protein levels, and that the characteristics of RSV persistence were preserved for over 87 passages. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Clinical Manifestations and Outcomes of West Nile Virus Infection

by James J. Sejvar

Viruses 2014, 6(2), 606-623; https://doi.org/10.3390/v6020606 - 6 Feb 2014

Cited by 179 | Viewed by 27222

Abstract

Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing [...] Read more.

Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing symptomatic illness, most develop a self-limited febrile illness. More severe illness with WNV (West Nile neuroinvasive disease, WNND) is manifested as meningitis, encephalitis or an acute anterior (polio) myelitis. These manifestations are generally more prevalent in older persons or those with immunosuppression. In the future, a more thorough understanding of the long-term physical, cognitive and functional outcomes of persons recovering from WNV illness will be important in understanding the overall illness burden. Full article

(This article belongs to the Special Issue West Nile Virus)

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Open AccessReview

Role of Human Cytomegalovirus Tegument Proteins in Virion Assembly

by Rebecca Marie Smith, Srivenkat Kosuri and Julie Anne Kerry

Viruses 2014, 6(2), 582-605; https://doi.org/10.3390/v6020582 - 6 Feb 2014

Cited by 19 | Viewed by 7314

Abstract

Like other herpesviruses, human cytomegalovirus (HCMV) contains a unique proteinaceous layer between the virion envelope and capsid, termed the tegument. Upon infection, the contents of the tegument layer are delivered to the host cell, along with the capsid and the viral genome, where [...] Read more.

Like other herpesviruses, human cytomegalovirus (HCMV) contains a unique proteinaceous layer between the virion envelope and capsid, termed the tegument. Upon infection, the contents of the tegument layer are delivered to the host cell, along with the capsid and the viral genome, where they facilitate the initial stages of virus replication. The tegument proteins also play important roles in virion assembly and this dual nature makes them attractive potential targets for antiviral therapies. While our knowledge regarding tegument protein function during the initiation of infection has been the subject of intense study, their roles in assembly are much less well understood. In this review, we will focus on recent studies that highlight the functions of HCMV tegument proteins during assembly, and pose key questions for further investigation. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessCommunication

Pretreatment of Mice with Oligonucleotide prop5 Protects Them from Influenza Virus Infections

by Kang Li, Zhe Zhou, Yu Ou Wang, Juan Liu, Hai Bao Zhao, Jing Yang and Sheng Qi Wang

Viruses 2014, 6(2), 573-581; https://doi.org/10.3390/v6020573 - 6 Feb 2014

Cited by 10 | Viewed by 6874

Abstract

Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5). In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of [...] Read more.

Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5). In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of influenza A virus in a mouse model. Prop5 intranasally administered the mice at dosages of 10 and 20 mg/kg/d at 24 h and 30 min before infection, provided 80% and 100% survival rates and prolonged mean survival days in comparison with influenza virus-infected mice (both p < 0.01). Moreover, viral titres in mice pretreated with prop5, at dose of 10 and 20 mg/kg/d, had declined significantly on day two, four, and six post-infection compared with the yields in infected mice (p < 0.05 or p < 0.01); lung index in mice pretreated with prop5 (20 mg/kg/d) had been inhibited on day six post-infection (p < 0.05). Western blotting and immunohistochemistry showed that prop5 could down-regulate the PDCD5 protein expression levels in lung tissues of infected mice. These data indicate that antisense oligonucleotide prop5 is a promising drug for prophylaxis and control influenza virus infections and provides an insight into the host-pathogen interaction. Full article

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

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Open AccessReview

CD81 and Hepatitis C Virus (HCV) Infection

by Lucie Fénéant, Shoshana Levy and Laurence Cocquerel

Viruses 2014, 6(2), 535-572; https://doi.org/10.3390/v6020535 - 6 Feb 2014

Cited by 80 | Viewed by 18326

Abstract

Hepatitis C Virus (HCV) infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of [...] Read more.

Hepatitis C Virus (HCV) infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of infection occurs through a complex multistep process involving a series of specific cellular entry factors. This process is likely mediated through the formation of a tightly orchestrated complex of HCV entry factors at the plasma membrane. Among HCV entry factors, the tetraspanin CD81 is one of the best characterized and it is undoubtedly a key player in the HCV lifecycle. In this review, we detail the current knowledge on the involvement of CD81 in the HCV lifecycle, as well as in the immune response to HCV infection. Full article

(This article belongs to the Special Issue Viruses and Tetraspanins)

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Open AccessArticle

Prevalence of Antibodies against Hantaviruses in Serum and Saliva of Adults Living or Working on Farms in Yorkshire, United Kingdom

by Lisa J. Jameson, Autilia Newton, Louise Coole, Edmund N. C. Newman, Miles W. Carroll, Nick J. Beeching, Roger Hewson and Robert M. Christley

Viruses 2014, 6(2), 524-534; https://doi.org/10.3390/v6020524 - 5 Feb 2014

Cited by 15 | Viewed by 6753

Abstract

Hantaviruses are an established cause of haemorrhagic fever with renal syndrome (HFRS) in Europe. Following a confirmed case of HFRS in the UK, in an individual residing on a farm in North Yorkshire and the Humber, a tidal estuary on the east coast [...] Read more.

Hantaviruses are an established cause of haemorrhagic fever with renal syndrome (HFRS) in Europe. Following a confirmed case of HFRS in the UK, in an individual residing on a farm in North Yorkshire and the Humber, a tidal estuary on the east coast of Northern England, and the subsequent isolation of a Seoul hantavirus from rats trapped on the patient’s farm, it was considered appropriate to further investigate the public health risk of this virus in the region. Of a total 119 individuals tested, nine (7.6%) were seropositive for hantavirus antibodies. Seven of the seropositive samples showed a stronger reaction to Seoul and Hantaan compared to other clinically relevant hantaviruses. Observation of rodents during the day, in particular mice, was associated with a reduced risk of seropositivity. In addition to one region known to be at risk following an acute case, five further potential risk areas have been identified. This study supports recently published evidence that hantaviruses are likely to be of public health interest in the region. Full article

(This article belongs to the Special Issue Hantaviruses)

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Open AccessArticle

Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

by Joseph Prescott, Blair L. DeBuysscher, Kyle S. Brown and Heinz Feldmann

Viruses 2014, 6(2), 516-523; https://doi.org/10.3390/v6020516 - 31 Jan 2014

Cited by 23 | Viewed by 7061

Abstract

Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has [...] Read more.

Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G). This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure), and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025), but animals were not significantly protected following 1 year of vaccination (p = 0.090). The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity. Full article

(This article belongs to the Special Issue Hantaviruses)

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Open AccessArticle

Analysis of an Outbreak of Hemorrhagic Fever with Renal Syndrome in College Students in Xi’an, China

by Chaofeng Ma, Zengguo Wang, Shen Li, Yuan Xing, Rui Wu, Jing Wei, Muhammad Nawaz, Huaiyu Tian, Bing Xu, Jingjun Wang and Pengbo Yu

Viruses 2014, 6(2), 507-515; https://doi.org/10.3390/v6020507 - 29 Jan 2014

Cited by 26 | Viewed by 7205

Abstract

The aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, in college students in the northern urban area of Xi’an in 2012. The outbreak affected six students and included two deaths. [...] Read more.

The aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, in college students in the northern urban area of Xi’an in 2012. The outbreak affected six students and included two deaths. The epidemiological survey revealed that both of the deceased cases were misdiagnosed initially, and treatment was delayed. Furthermore, a higher rodent population density and lower HFRS vaccine coverage were observed in the affected area, which indicates a possible role in the outbreak. Rattus norvegicus (Rn) and Mus musculus (Mm) were the predominant host populations in the area. Genotyping revealed that all HVs from patients and rodents were Hantaan virus (HTNV). Sequence analysis of the S segments revealed that the HTNVs reported in this study had high similarity with strains reported in 2011 and 1985, but these viruses diverged from a strain isolated in 1984 and the HTNV prototype strain 76-118. Detection of anti-HV IgG and amplification of the S segment of HTNV from a non-natural HTNV reservoir indicates that further investigations by increased rodent trapping are necessary. Full article

(This article belongs to the Special Issue Hantaviruses)

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Open AccessArticle

Structural Analyses of Avocado sunblotch viroid Reveal Differences in the Folding of Plus and Minus RNA Strands

by Clémentine Delan-Forino, Jules Deforges, Lionel Benard, Bruno Sargueil, Marie-Christine Maurel and Claire Torchet

Viruses 2014, 6(2), 489-506; https://doi.org/10.3390/v6020489 - 29 Jan 2014

Cited by 17 | Viewed by 8870

Abstract

Viroids are small pathogenic circular single-stranded RNAs, present in two complementary sequences, named plus and minus, in infected plant cells. A high degree of complementarities between different regions of the RNAs allows them to adopt complex structures. Since viroids are naked non-coding RNAs, [...] Read more.

Viroids are small pathogenic circular single-stranded RNAs, present in two complementary sequences, named plus and minus, in infected plant cells. A high degree of complementarities between different regions of the RNAs allows them to adopt complex structures. Since viroids are naked non-coding RNAs, interactions with host factors appear to be closely related to their structural and catalytic characteristics. Avocado sunblotch viroid (ASBVd), a member of the family Avsunviroidae, replicates via a symmetric RNA-dependant rolling-circle process, involving self-cleavage via hammerhead ribozymes. Consequently, it is assumed that ASBVd plus and minus strands adopt similar structures. Moreover, by computer analyses, a quasi-rod-like secondary structure has been predicted. Nevertheless, secondary and tertiary structures of both polarities of ASBVd remain unsolved. In this study, we analyzed the characteristic of each strand of ASBVd through biophysical analyses. We report that ASBVd transcripts of plus and minus polarities exhibit differences in electrophoretic mobility under native conditions and in thermal denaturation profiles. Subsequently, the secondary structures of plus and minus polarities of ASBVd were probed using the RNA-selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) method. The models obtained show that both polarities fold into different structures. Moreover, our results suggest the existence of a kissing-loop interaction within the minus strand that may play a role in in vivo viroid life cycle. Full article

(This article belongs to the Special Issue Plant Viruses)

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Open AccessArticle

Human Cytomegalovirus UL34 Early and Late Proteins Are Essential for Viral Replication

by Rico Rana and Bonita J. Biegalke

Viruses 2014, 6(2), 476-488; https://doi.org/10.3390/v6020476 - 28 Jan 2014

Cited by 9 | Viewed by 6916

Abstract

UL34 is one of the ~50 genes of human cytomegalovirus (HCMV) required for replication in cell culture in human fibroblasts. UL34 encodes highly related early (UL34a) and late (UL34b) proteins that are virtually identical, with the early protein containing an additional 21 amino [...] Read more.

UL34 is one of the ~50 genes of human cytomegalovirus (HCMV) required for replication in cell culture in human fibroblasts. UL34 encodes highly related early (UL34a) and late (UL34b) proteins that are virtually identical, with the early protein containing an additional 21 amino terminal amino acids. The UL34 proteins are sequence-specific DNA‑binding proteins that localize to the nucleus. The HCMV genome contains 14 to 15 UL34 binding sites; two of the UL34 binding sites contribute to transcriptional regulation of two other viral genes, US3 and US9. The roles of the remaining binding sites and the requirement for both UL34 proteins during viral infection remain unknown. We examined the contributions of the early and late UL34 proteins to viral replication by generating HCMV-containing bacterial artificial chromosomes with the initiation codon for the early or the late protein mutated. Neither virus was able to replicate, demonstrating that UL34 expression is required throughout the viral replication cycle. A marked decrease in viral gene expression for each of the mutants suggests that UL34 proteins may contribute generally to transcriptional regulation. Intracellular localization studies demonstrated that UL34 colocalizes with the major immediate early protein, IE2, and the viral DNA polymerase processivity factor, UL44, to viral DNA replication centers. In conclusion, sustained UL34 protein expression is required for viral replication. The sequence-specific DNA binding ability of UL34 proteins, their localization to viral DNA replication centers and their general effects on viral gene expressions suggests that UL34 proteins contribute to the establishment of a nuclear environment necessary for viral gene expression and DNA replication. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessArticle

Molecular and Biological Characterization of a New Isolate of Guinea Pig Cytomegalovirus

by Mark R. Schleiss, Shane McAllister, Anibal G. Armién, Nelmary Hernandez-Alvarado, Claudia Fernández-Alarcón, Jason C. Zabeli, Thiruvarangan Ramaraj, John A. Crow and Michael A. McVoy

Viruses 2014, 6(2), 448-475; https://doi.org/10.3390/v6020448 - 27 Jan 2014

Cited by 10 | Viewed by 7758

Abstract

Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally be undertaken in a [...] Read more.

Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally be undertaken in a small animal model, such as the guinea pig cytomegalovirus (GPCMV) model, prior to human clinical trials. However, the ability to model re-infection in the GPCMV model has been limited by availability of only one strain of virus, the 22122 strain, isolated in 1957. In this report, we describe the isolation of a new GPCMV strain, the CIDMTR strain. This strain demonstrated morphological characteristics of a typical Herpesvirinae by electron microscopy. Illumina and PacBio sequencing demonstrated a genome of 232,778 nt. Novel open reading frames ORFs not found in reference strain 22122 included an additional MHC Class I homolog near the right genome terminus. The CIDMTR strain was capable of dissemination in immune compromised guinea pigs, and was found to be capable of congenital transmission in GPCMV-immune dams previously infected with salivary gland‑adapted strain 22122 virus. The availability of a new GPCMV strain should facilitate study of re-infection in this small animal model. Full article

(This article belongs to the Special Issue Recent CMV Research)

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Open AccessReview

Passive Immunization against HIV/AIDS by Antibody Gene Transfer

by Lili Yang and Pin Wang

Viruses 2014, 6(2), 428-447; https://doi.org/10.3390/v6020428 - 27 Jan 2014

Cited by 13 | Viewed by 12924

Abstract

Despite tremendous efforts over the course of many years, the quest for an effective HIV vaccine by the classical method of active immunization remains largely elusive. However, two recent studies in mice and macaques have now demonstrated a new strategy designated as Vectored [...] Read more.

Despite tremendous efforts over the course of many years, the quest for an effective HIV vaccine by the classical method of active immunization remains largely elusive. However, two recent studies in mice and macaques have now demonstrated a new strategy designated as Vectored ImmunoProphylaxis (VIP), which involves passive immunization by viral vector-mediated delivery of genes encoding broadly neutralizing antibodies (bnAbs) for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing antibodies. This unorthodox approach raises new promise for combating the ongoing global HIV pandemic. In this article, we survey the status of antibody gene transfer, review the revolutionary progress on isolation of extremely bnAbs, detail VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics. Full article

(This article belongs to the Special Issue Gene Therapy for Retroviral Infections)

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Open AccessReview

Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

by Justin A. Roby, Gorben P. Pijlman, Jeffrey Wilusz and Alexander A. Khromykh

Viruses 2014, 6(2), 404-427; https://doi.org/10.3390/v6020404 - 27 Jan 2014

Cited by 126 | Viewed by 16078

Abstract

Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested [...] Read more.

Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated. Full article

(This article belongs to the Special Issue West Nile Virus)

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Open AccessCommunication

Pseudo-Mannosylated DC-SIGN Ligands as Potential Adjuvants for HIV Vaccines

by Angela Berzi, Norbert Varga, Sara Sattin, Patrizio Antonazzo, Mara Biasin, Irene Cetin, Daria Trabattoni, Anna Bernardi and Mario Clerici

Viruses 2014, 6(2), 391-403; https://doi.org/10.3390/v6020391 - 27 Jan 2014

Cited by 23 | Viewed by 7965

Abstract

The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs). Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary [...] Read more.

The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs). Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19) to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated. Full article

(This article belongs to the Special Issue AIDS Vaccine 2014)

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Open AccessReview

HSV-2 Vaccine: Current Status and Insight into Factors for Developing an Efficient Vaccine

by Xiao-Peng Zhu, Zaka S. Muhammad, Jian-Guang Wang, Wu Lin, Shi-Kun Guo and Wei Zhang

Viruses 2014, 6(2), 371-390; https://doi.org/10.3390/v6020371 - 24 Jan 2014

Cited by 39 | Viewed by 12454

Abstract

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate [...] Read more.

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Viruses, Volume 6, Issue 2 (February 2014) – 30 articles , Pages 371-950

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