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Viruses, Volume 6, Issue 3 (March 2014), Pages 951-1472

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Editorial

Jump to: Research, Review

Open AccessEditorial Acknowledgement to Reviewers of Viruses in 2013
Viruses 2014, 6(3), 1073-1077; doi:10.3390/v6031073
Received: 5 March 2014 / Accepted: 5 March 2014 / Published: 5 March 2014
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Abstract The editors of Viruses would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013. [...] Full article

Research

Jump to: Editorial, Review

Open AccessArticle Modulation of Homology-Directed Repair in T98G Glioblastoma Cells Due to Interactions between Wildtype p53, Rad51 and HCMV IE1-72
Viruses 2014, 6(3), 968-985; doi:10.3390/v6030968
Received: 24 January 2014 / Revised: 15 February 2014 / Accepted: 17 February 2014 / Published: 26 February 2014
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Abstract
Human cytomegalovirus (HCMV) is a ubiquitous pathogen capable of causing life threatening consequences in neonates and immune-compromised individuals. HCMV inflicts site-specific double strand breaks (DSBs) in the cellular genome. DNA damage infliction raises the corollary question of virus modulation of DNA repair. [...] Read more.
Human cytomegalovirus (HCMV) is a ubiquitous pathogen capable of causing life threatening consequences in neonates and immune-compromised individuals. HCMV inflicts site-specific double strand breaks (DSBs) in the cellular genome. DNA damage infliction raises the corollary question of virus modulation of DNA repair. We recently reported HDR was stimulated in wt human foreskin fibroblasts (HFFs) during fully permissive infection or expression of the HCMV protein IE1-72 (IE72). These studies have been extended into semi-permissive T98G glioblastoma cells. T98Gs encode a mutant p53, which may contribute to their high baseline rate of HDR. We fully expected HCMV infection to increase HDR in T98Gs, similar to its effects in HFFs. Surprisingly in T98Gs HCMV infection, or sole expression of IE72, decreased HDR by two-fold. Transient expression of wt p53 in T98Gs also reduced HDR by two-fold. Dual transient expression of wt p53 and IE72 restored high baseline HDR levels. GST pulldown experiments revealed that both IE72 and wt p53 bound the important HDR protein, Rad51. We conclude that the expression of certain HCMV proteins can modulate HDR in an infected cell, dependent upon p53 status. We propose a model of the protein interactions explaining this behavior. Full article
(This article belongs to the Special Issue Recent CMV Research) Print Edition available
Open AccessArticle Hantavirus Public Health Outreach Effectiveness in Three Populations: An Overview of Northwestern New Mexico, Los Santos Panama, and Region IX Chile
Viruses 2014, 6(3), 986-1003; doi:10.3390/v6030986
Received: 9 December 2013 / Revised: 13 January 2014 / Accepted: 18 February 2014 / Published: 27 February 2014
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Abstract
This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS) outreach programs in New Mexico, Panama, and Chile. Understanding the role of human demographics, disease ecology, and human behavior in the disease process is critical to the examination of community responses in [...] Read more.
This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS) outreach programs in New Mexico, Panama, and Chile. Understanding the role of human demographics, disease ecology, and human behavior in the disease process is critical to the examination of community responses in terms of behavior changes. Attitudes, knowledge, and behavior across three populations were measured through the implementation of a self-administered questionnaire (N = 601). Surveys implemented in Chile and Panama in 2004, followed by northwestern New Mexico in 2008, attempted to assess knowledge and behavior change with respect to hantavirus in high- and lower-risk prevalence areas during endemic periods. While levels of concern over contracting hantavirus were lowest in New Mexico, they were highest in Panama. Respondents in Chile showed mid-level concern and exhibited a tendency to practice proper cleaning methods more than in New Mexico and Panama. This indicates that public health messages appear to be more effective in Chile. However, since negative behavior changes, such as sweeping and vacuuming, occur at some level in all three populations, improved messages should help decrease risk of exposure to HPS. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China
Viruses 2014, 6(3), 1004-1014; doi:10.3390/v6031004
Received: 10 November 2013 / Revised: 26 January 2014 / Accepted: 20 February 2014 / Published: 28 February 2014
Cited by 1 | PDF Full-text (1273 KB) | HTML Full-text | XML Full-text
Abstract
In 2012, an FHV-1-like virus was isolated from a tiger that presented with clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was performed with the FK81 cell line, and the virus was identified by PCR, transmission electron microscopy (TEM), and the [...] Read more.
In 2012, an FHV-1-like virus was isolated from a tiger that presented with clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was performed with the FK81 cell line, and the virus was identified by PCR, transmission electron microscopy (TEM), and the phylogenetic analysis of the partial thymidine kinase (TK) and glycoprotein B (gB) genes. A total of 253 bp of the TK gene and 566 bp of the gB gene were amplified from the trachea of the tiger by PCR/RT-PCR method. Phylogenetic analysis showed that the isolate belonged to the same cluster with other FHV-1 strains obtained from GenBank. Herpes-like viruses with an envelope and diameters of approximately 200 nm were observed in the culture supernatants of FK81 cells inoculated with samples from the tiger. The FHV-1 infection was confirmed by an animal challenge experiment in a cat model. Our finding extends the host range of FHV-1 and has implications for FHV-1 infection and South China tiger conservation. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle Development of Lectin-Linked Immunomagnetic Separation for the Detection of Hepatitis A Virus
Viruses 2014, 6(3), 1037-1048; doi:10.3390/v6031037
Received: 9 September 2013 / Revised: 14 January 2014 / Accepted: 17 January 2014 / Published: 4 March 2014
Cited by 3 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text
Abstract
The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus [...] Read more.
The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus to cells. In this study, we initially investigated the effects of pH (4.0–10.0) and metal ions (Fe2+, Co2+, Cu2+, Mg2+, K+, and Ca2+) on the binding of HAV to oyster digestive cells. The lowest relative binding (RB) of HAV to the cells was found at pH 4.0 and in FeSO4 solution (64.6% and 68.1%, respectively). To develop an alternative to antibody-dependent immunomagnetic separation prior to detection of HAV using RT-PCR, the binding of HAV to five lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Ulex europaeus agglutinin (UEA-1) and soybean agglutinin (SBA), was evaluated using ELISAs. SBA showed significantly higher RB to HAV than the other lectins tested. In addition, HAV could be concentrated within 30 min using SBA-linked magnetic bead separation (SMS) prior to the RT-PCR assay. Our findings demonstrate the feasibility of using SMS combined with RT-PCR to detect HAV at dilutions ranging from 10−1–10−4 of a HAV stock (titer: 104 TCID50/mL). Full article
(This article belongs to the Section Animal Viruses)
Open AccessCommunication Evidence Showing that Tetraspanins Inhibit HIV-1-Induced Cell-Cell Fusion at a Post-Hemifusion Stage
Viruses 2014, 6(3), 1078-1090; doi:10.3390/v6031078
Received: 8 January 2014 / Revised: 14 February 2014 / Accepted: 20 February 2014 / Published: 7 March 2014
Cited by 5 | PDF Full-text (1415 KB) | HTML Full-text | XML Full-text
Abstract
Human immunodeficiency virus type 1 (HIV-1) transmission takes place primarily through cell-cell contacts known as virological synapses. Formation of these transient adhesions between infected and uninfected cells can lead to transmission of viral particles followed by separation of the cells. Alternatively, the [...] Read more.
Human immunodeficiency virus type 1 (HIV-1) transmission takes place primarily through cell-cell contacts known as virological synapses. Formation of these transient adhesions between infected and uninfected cells can lead to transmission of viral particles followed by separation of the cells. Alternatively, the cells can fuse, thus forming a syncytium. Tetraspanins, small scaffolding proteins that are enriched in HIV-1 virions and actively recruited to viral assembly sites, have been found to negatively regulate HIV-1 Env-induced cell-cell fusion. How these transmembrane proteins inhibit membrane fusion, however, is currently not known. As a first step towards elucidating the mechanism of fusion repression by tetraspanins, e.g., CD9 and CD63, we sought to identify the stage of the fusion process during which they operate. Using a chemical epistasis approach, four fusion inhibitors were employed in tandem with CD9 overexpression. Cells overexpressing CD9 were found to be sensitized to inhibitors targeting the pre-hairpin and hemifusion intermediates, while they were desensitized to an inhibitor of the pore expansion stage. Together with the results of a microscopy-based dye transfer assay, which revealed CD9- and CD63-induced hemifusion arrest, our investigations strongly suggest that tetraspanins block HIV-1-induced cell-cell fusion at the transition from hemifusion to pore opening. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
Figures

Open AccessArticle Equilibrium and Kinetics of Sin Nombre Hantavirus Binding at DAF/CD55 Functionalized Bead Surfaces
Viruses 2014, 6(3), 1091-1111; doi:10.3390/v6031091
Received: 30 November 2013 / Revised: 13 February 2014 / Accepted: 23 February 2014 / Published: 10 March 2014
Cited by 5 | PDF Full-text (1742 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc [...] Read more.
Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized DAF ((DAF)2-Fc). When mixed with Protein G beads the resulting DAF beads can be used as a generalizable platform for measuring kinetic and equilibrium binding constants of DAF binding targets. The hantavirus interaction has high affinity (24–30 nM; kon ~ 105 M−1s−1, koff ~ 0.0045 s−1). The bivalent (DAF)2-Fc/SNV data agree with hantavirus binding to DAF expressed on Tanoue B cells (Kd = 14.0 nM). Monovalent affinity interaction between SNV and recombinant DAF of 58.0 nM is determined from competition binding. This study serves a dual purpose of presenting a convenient and quantitative approach of measuring binding affinities between DAF and the many cognate viral and bacterial ligands and providing new data on the binding constant of DAF and Sin Nombre hantavirus. Knowledge of the equilibrium binding constant allows for the determination of the relative fractions of bound and free virus particles in cell entry assays. This is important for drug discovery assays for cell entry inhibitors. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Changes in Diversification Patterns and Signatures of Selection during the Evolution of Murinae-Associated Hantaviruses
Viruses 2014, 6(3), 1112-1134; doi:10.3390/v6031112
Received: 29 November 2013 / Revised: 19 February 2014 / Accepted: 24 February 2014 / Published: 10 March 2014
Cited by 4 | PDF Full-text (1005 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the last 50 years, hantaviruses have significantly affected public health worldwide, but the exact extent of the distribution of hantavirus diseases, species and lineages and the risk of their emergence into new geographic areas are still poorly known. In particular, the [...] Read more.
In the last 50 years, hantaviruses have significantly affected public health worldwide, but the exact extent of the distribution of hantavirus diseases, species and lineages and the risk of their emergence into new geographic areas are still poorly known. In particular, the determinants of molecular evolution of hantaviruses circulating in different geographical areas or different host species are poorly documented. Yet, this understanding is essential for the establishment of more accurate scenarios of hantavirus emergence under different climatic and environmental constraints. In this study, we focused on Murinae-associated hantaviruses (mainly Seoul Dobrava and Hantaan virus) using sequences available in GenBank and conducted several complementary phylogenetic inferences. We sought for signatures of selection and changes in patterns and rates of diversification in order to characterize hantaviruses’ molecular evolution at different geographical scales (global and local). We then investigated whether these events were localized in particular geographic areas. Our phylogenetic analyses supported the assumption that RNA virus molecular variations were under strong evolutionary constraints and revealed changes in patterns of diversification during the evolutionary history of hantaviruses. These analyses provide new knowledge on the molecular evolution of hantaviruses at different scales of time and space. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Murine Leukemia Virus Uses TREX Components for Efficient Nuclear Export of Unspliced Viral Transcripts
Viruses 2014, 6(3), 1135-1148; doi:10.3390/v6031135
Received: 12 December 2013 / Revised: 21 February 2014 / Accepted: 25 February 2014 / Published: 10 March 2014
Cited by 3 | PDF Full-text (460 KB) | HTML Full-text | XML Full-text
Abstract
Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV) transcripts depends on the nuclear export factor (NXF1) pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the [...] Read more.
Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV) transcripts depends on the nuclear export factor (NXF1) pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the NXF1-mediated nuclear export of cellular mRNAs, its contribution to the export of MLV mRNA transcripts remains poorly understood. Here, we studied the involvement of TREX components in the export of MLV transcripts. Depletion of UAP56, but not Aly/REF, reduced the level of both unspliced and spliced viral transcripts in the cytoplasm. Interestingly, depletion of THO components, including THOC5 and THOC7, affected only unspliced viral transcripts in the cytoplasm. Moreover, the RNA immunoprecipitation assay showed that only the unspliced viral transcript interacted with THOC5. These results imply that MLV requires UAP56, THOC5 and THOC7, in addition to NXF1, for nuclear export of viral transcripts. Given that naturally intronless mRNAs, but not bulk mRNAs, require THOC5 for nuclear export, it is plausible that THOC5 plays a key role in the export of unspliced MLV transcripts. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle Chronic Bee Paralysis Virus in Honeybee Queens: Evaluating Susceptibility and Infection Routes
Viruses 2014, 6(3), 1188-1201; doi:10.3390/v6031188
Received: 21 January 2014 / Revised: 4 March 2014 / Accepted: 5 March 2014 / Published: 11 March 2014
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Abstract
Chronic bee paralysis virus (CBPV) is known as a disease of worker honey bees. To investigate pathogenesis of the CBPV on the queen, the sole reproductive individual in a colony, we conducted experiments regarding the susceptibility of queens to CBPV. Results from [...] Read more.
Chronic bee paralysis virus (CBPV) is known as a disease of worker honey bees. To investigate pathogenesis of the CBPV on the queen, the sole reproductive individual in a colony, we conducted experiments regarding the susceptibility of queens to CBPV. Results from susceptibility experiment showed a similar disease progress in the queens compared to worker bees after infection. Infected queens exhibit symptoms by Day 6 post infection and virus levels reach 1011 copies per head. In a transmission experiment we showed that social interactions may affect the disease progression. Queens with forced contact to symptomatic worker bees acquired an overt infection with up to 1011 virus copies per head in six days. In contrast, queens in contact with symptomatic worker bees, but with a chance to receive food from healthy bees outside the cage appeared healthy. The virus loads did not exceed 107 in the majority of these queens after nine days. Symptomatic worker bees may transmit sufficient active CBPV particles to the queen through trophallaxis, to cause an overt infection. Full article
(This article belongs to the Section Insect Viruses)
Open AccessArticle Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination
Viruses 2014, 6(3), 1202-1218; doi:10.3390/v6031202
Received: 20 January 2014 / Revised: 1 March 2014 / Accepted: 4 March 2014 / Published: 12 March 2014
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Abstract
Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, [...] Read more.
Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28YFP expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAGYFP in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28YFP protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28YFP is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the DUS28 virus (TB40/E-FLAGYFP) generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAGYFP (DUS28) displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus. Full article
(This article belongs to the Special Issue Recent CMV Research) Print Edition available
Open AccessArticle Viral Metagenomics: Analysis of Begomoviruses by Illumina High-Throughput Sequencing
Viruses 2014, 6(3), 1219-1236; doi:10.3390/v6031219
Received: 14 October 2013 / Revised: 12 February 2014 / Accepted: 20 February 2014 / Published: 12 March 2014
Cited by 13 | PDF Full-text (678 KB) | HTML Full-text | XML Full-text
Abstract
Traditional DNA sequencing methods are inefficient, lack the ability to discern the least abundant viral sequences, and ineffective for determining the extent of variability in viral populations. Here, populations of single-stranded DNA plant begomoviral genomes and their associated beta- and alpha-satellite molecules [...] Read more.
Traditional DNA sequencing methods are inefficient, lack the ability to discern the least abundant viral sequences, and ineffective for determining the extent of variability in viral populations. Here, populations of single-stranded DNA plant begomoviral genomes and their associated beta- and alpha-satellite molecules (virus-satellite complexes) (genus, Begomovirus; family, Geminiviridae) were enriched from total nucleic acids isolated from symptomatic, field-infected plants, using rolling circle amplification (RCA). Enriched virus-satellite complexes were subjected to Illumina-Next Generation Sequencing (NGS). CASAVA and SeqMan NGen programs were implemented, respectively, for quality control and for de novo and reference-guided contig assembly of viral-satellite sequences. The authenticity of the begomoviral sequences, and the reproducibility of the Illumina-NGS approach for begomoviral deep sequencing projects, were validated by comparing NGS results with those obtained using traditional molecular cloning and Sanger sequencing of viral components and satellite DNAs, also enriched by RCA or amplified by polymerase chain reaction. As the use of NGS approaches, together with advances in software development, make possible deep sequence coverage at a lower cost; the approach described herein will streamline the exploration of begomovirus diversity and population structure from naturally infected plants, irrespective of viral abundance. This is the first report of the implementation of Illumina-NGS to explore the diversity and identify begomoviral-satellite SNPs directly from plants naturally-infected with begomoviruses under field conditions. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protoza)
Open AccessArticle Construction of Eukaryotic Expression Vector with mBD1-mBD3 Fusion Genes and Exploring Its Activity against Influenza A Virus
Viruses 2014, 6(3), 1237-1252; doi:10.3390/v6031237
Received: 29 November 2013 / Revised: 11 February 2014 / Accepted: 24 February 2014 / Published: 13 March 2014
Cited by 2 | PDF Full-text (832 KB) | HTML Full-text | XML Full-text
Abstract
Influenza (flu) pandemics have exhibited a great threat to human health throughout history. With the emergence of drug-resistant strains of influenza A virus (IAV), it is necessary to look for new agents for treatment and transmission prevention of the flu. Defensins are [...] Read more.
Influenza (flu) pandemics have exhibited a great threat to human health throughout history. With the emergence of drug-resistant strains of influenza A virus (IAV), it is necessary to look for new agents for treatment and transmission prevention of the flu. Defensins are small (2–6 kDa) cationic peptides known for their broad-spectrum antimicrobial activity. Beta-defensins (β-defensins) are mainly produced by barrier epithelial cells and play an important role in attacking microbe invasion by epithelium. In this study, we focused on the anti-influenza A virus activity of mouse β-defensin 1 (mBD1) and β defensin-3 (mBD3) by synthesizing their fusion peptide with standard recombinant methods. The eukaryotic expression vectors pcDNA3.1(+)/mBD1-mBD3 were constructed successfully by overlap-PCR and transfected into Madin-Darby canine kidney (MDCK) cells. The MDCK cells transfected by pcDNA3.1(+)/mBD1-mBD3 were obtained by G418 screening, and the mBD1-mBD3 stable expression pattern was confirmed in MDCK cells by RT-PCR and immunofluorescence assay. The acquired stable transfected MDCK cells were infected with IAV (A/PR/8/34, H1N1, 0.1 MOI) subsequently and the virus titers in cell culture supernatants were analyzed by TCID50 72 h later. The TCID50 titer of the experimental group was clearly lower than that of the control group (p < 0.001). Furthermore, BALB/C mice were injected with liposome-encapsulated pcDNA3.1(+)/mBD1-mBD3 through muscle and then challenged with the A/PR/8/34 virus. Results showed the survival rate of 100% and lung index inhibitory rate of 32.6% in pcDNA3.1(+)/mBD1-mBD3group; the TCID50 titer of lung homogenates was clearly lower than that of the control group (p < 0.001). This study demonstrates that mBD1-mBD3 expressed by the recombinant plasmid pcDNA3.1(+)/mBD1-mBD3 could inhibit influenza A virus replication both in vitro and in vivo. These observations suggested that the recombinant mBD1-mBD3 might be developed into an agent for influenza prevention and treatment. Full article
(This article belongs to the Section Antivirals & Vaccines)
Open AccessArticle Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus
Viruses 2014, 6(3), 1253-1273; doi:10.3390/v6031253
Received: 26 November 2013 / Revised: 24 February 2014 / Accepted: 5 March 2014 / Published: 13 March 2014
Cited by 2 | PDF Full-text (2127 KB) | HTML Full-text | XML Full-text
Abstract
The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection [...] Read more.
The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection and transfection showed that N protein was predominately localized in the cytoplasm, but also found in the nucleolus in Vero E6 cells. Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. We also identified two nuclear export signals (NES, aa221–236, and 325–364), however, only the nuclear export signal (aa325–364) was found to be functional in the context of the full-length N protein. Finally, the activity of this nuclear export signal (NES) was inhibited by the antibiotic Lepomycin B, suggesting that N is exported by a chromosome region maintenance 1-related export pathway. Full article
(This article belongs to the Special Issue Animal Arteriviruses and Coronaviruses)
Open AccessArticle Hepatitis A Immunity in the District of Aveiro (Portugal): An Eleven-Year Surveillance Study (2002–2012)
Viruses 2014, 6(3), 1336-1345; doi:10.3390/v6031336
Received: 10 January 2014 / Revised: 19 February 2014 / Accepted: 20 February 2014 / Published: 14 March 2014
Cited by 1 | PDF Full-text (686 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis A is a common viral liver disease and brings serious health and economic problems as its epidemiologic pattern changes over time. National serosurveys from developed countries have indicated a decline in HAV (hepatitis A virus) seroprevalence over time due to the [...] Read more.
Hepatitis A is a common viral liver disease and brings serious health and economic problems as its epidemiologic pattern changes over time. National serosurveys from developed countries have indicated a decline in HAV (hepatitis A virus) seroprevalence over time due to the improvement of economic and sanitation levels. The hepatitis A virus (HAV) immunity rate was surveyed throughout an eleven-year period by sex and age group in Aveiro District. In this retrospective study, blood samples from patients of Aveiro District, in ambulatory regime, collected at the Clinical Analysis Laboratory Avelab between 2002 and 2012 were screened for the presence of antibodies against HAV antigen using a chemiluminescence immunoassay. The global immunity (positive total anti-HAV) was 60% and only 0.3% of the patients presented recent infection by HAV (positive IgM anti-HAV). The HAV immunity was age-dependent (p < 0.05), but no significant differences (p > 0.05) between sexes were observed. The immunity was similar throughout the study period (p > 0.05). The results of this study indicate that young people (especially under 25 years old) from District of Aveiro are susceptible to HAV infection, constituting a high risk group. The elderly should be also a concern in the future of Hepatitis A infection. Full article
(This article belongs to the Section Animal Viruses)
Figures

Open AccessArticle HCMV Infection of Human Trophoblast Progenitor Cells of the Placenta Is Neutralized by a Human Monoclonal Antibody to Glycoprotein B and Not by Antibodies to the Pentamer Complex
Viruses 2014, 6(3), 1346-1364; doi:10.3390/v6031346
Received: 22 January 2014 / Revised: 27 February 2014 / Accepted: 27 February 2014 / Published: 19 March 2014
Cited by 12 | PDF Full-text (2129 KB) | HTML Full-text | XML Full-text
Abstract
Human cytomegalovirus (HCMV) is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a [...] Read more.
Human cytomegalovirus (HCMV) is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs), the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs) give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs). Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A) showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb), TRL345, reactive with glycoprotein B (gB), but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease. Full article
(This article belongs to the Special Issue Recent CMV Research) Print Edition available
Open AccessArticle Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge
Viruses 2014, 6(3), 1410-1423; doi:10.3390/v6031410
Received: 7 February 2014 / Revised: 13 March 2014 / Accepted: 14 March 2014 / Published: 24 March 2014
Cited by 2 | PDF Full-text (527 KB) | HTML Full-text | XML Full-text
Abstract
Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or [...] Read more.
Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life), as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity. Full article
(This article belongs to the Section Antivirals & Vaccines)
Open AccessArticle IFN-Dependent and -Independent Reduction in West Nile Virus Infectivity in Human Dermal Fibroblasts
Viruses 2014, 6(3), 1424-1441; doi:10.3390/v6031424
Received: 22 January 2014 / Revised: 5 March 2014 / Accepted: 7 March 2014 / Published: 24 March 2014
Cited by 5 | PDF Full-text (1027 KB) | HTML Full-text | XML Full-text
Abstract
Although dermal fibroblasts are one of the first cell types exposed to West Nile virus (WNV) during a blood meal by an infected mosquito, little is known about WNV replication within this cell type. Here, we demonstrate that neuroinvasive, WNV-New York (WNV-NY), [...] Read more.
Although dermal fibroblasts are one of the first cell types exposed to West Nile virus (WNV) during a blood meal by an infected mosquito, little is known about WNV replication within this cell type. Here, we demonstrate that neuroinvasive, WNV-New York (WNV-NY), and nonneuroinvasive, WNV-Australia (WNV-AUS60) strains are able to infect and replicate in primary human dermal fibroblasts (HDFs). However, WNV-AUS60 replication and spread within HDFs was reduced compared to that of WNV-NY due to an interferon (IFN)-independent reduction in viral infectivity early in infection. Additionally, replication of both strains was constrained late in infection by an IFN-β-dependent reduction in particle infectivity. Overall, our data indicates that human dermal fibroblasts are capable of supporting WNV replication; however, the low infectivity of particles produced from HDFs late in infection suggests that this cell type likely plays a limited role as a viral reservoir in vivo. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle Retrospective Serology Study of Respiratory Virus Infections in Captive Great Apes
Viruses 2014, 6(3), 1442-1453; doi:10.3390/v6031442
Received: 23 December 2013 / Revised: 14 March 2014 / Accepted: 17 March 2014 / Published: 24 March 2014
Cited by 3 | PDF Full-text (734 KB) | HTML Full-text | XML Full-text
Abstract
Great apes are extremely sensitive to infections with human respiratory viruses. In this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. More than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the [...] Read more.
Great apes are extremely sensitive to infections with human respiratory viruses. In this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. More than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the human respiratory viruses RSV (respiratory syncytial virus, hMPV (human metapneumovirus), H1N1 and H3N2 influenza A viruses, and influenza B virus. In all ape species high seroprevalences were found for RSV, hMPV, and influenza B virus. A high percentage of captive chimpanzees also showed evidence of influenza A H1N1 infections, and had low levels of H3N2 antibodies, while in sera from gorillas and orang-utans antibody levels to influenza A and B viruses were much lower or practically absent. Transmission of respiratory viruses was examined in longitudinal sera of young chimpanzees, and in chimpanzee sera taken during health checks. In young animals isolated cases of influenza infections were monitored, but evidence was found for single introductions followed by a rapid dissemination of RSV and hMPV within the group. Implementation of strict guidelines for handling and housing of nonhuman primates was shown to be an efficient method to reduce the introduction of respiratory infections in colonies of captive animals. RSV seroprevalence rates of chimpanzees remained high, probably due to circulating virus in the chimpanzee colony. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle A Role for CD81 and Hepatitis C Virus in Hepatoma Mobility
Viruses 2014, 6(3), 1454-1472; doi:10.3390/v6031454
Received: 12 December 2013 / Revised: 27 January 2014 / Accepted: 5 March 2014 / Published: 24 March 2014
Cited by 2 | PDF Full-text (2604 KB) | HTML Full-text | XML Full-text
Abstract
Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs) that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC) is an increasing global [...] Read more.
Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs) that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC) is an increasing global health burden, in part due to the increasing prevalence of hepatitis C virus (HCV) associated HCC. The tetraspanin CD81 is an essential receptor for HCV, however, its role in hepatoma biology is uncertain. We demonstrate that antibody engagement of CD81 promotes hepatoma spread, which is limited by HCV infection, in an actin-dependent manner and identify an essential role for the C-terminal interaction with Ezrin-Radixin-Moesin (ERM) proteins in this process. We show enhanced hepatoma migration and invasion following expression of CD81 and a reduction in invasive potential upon CD81 silencing. In addition, we reveal poorly differentiated HCC express significantly higher levels of CD81 compared to adjacent non-tumor tissue. In summary, these data support a role for CD81 in regulating hepatoma mobility and propose CD81 as a tumour promoter. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)

Review

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Open AccessReview More Novel Hantaviruses and Diversifying Reservoir Hosts — Time for Development of Reservoir-Derived Cell Culture Models?
Viruses 2014, 6(3), 951-967; doi:10.3390/v6030951
Received: 12 December 2013 / Revised: 11 February 2014 / Accepted: 15 February 2014 / Published: 26 February 2014
Cited by 5 | PDF Full-text (718 KB) | HTML Full-text | XML Full-text
Abstract
Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla [...] Read more.
Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview B Cell Response and Mechanisms of Antibody Protection to West Nile Virus
Viruses 2014, 6(3), 1015-1036; doi:10.3390/v6031015
Received: 17 December 2013 / Revised: 7 February 2014 / Accepted: 8 February 2014 / Published: 3 March 2014
Cited by 2 | PDF Full-text (1370 KB) | HTML Full-text | XML Full-text
Abstract
West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several [...] Read more.
West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several candidates in clinical trials, there are no approved vaccines or WNV-specific therapies for the treatment of WNV disease in humans. From studies with small animal models and convalescent human patients, a great deal has been learned concerning the immune response to infection with WNV. Here, we provide an overview of a subset of that information regarding the humoral and antibody response generated during WNV infection. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Genomic and Functional Characteristics of Human Cytomegalovirus Revealed by Next-Generation Sequencing
Viruses 2014, 6(3), 1049-1072; doi:10.3390/v6031049
Received: 20 January 2014 / Revised: 11 February 2014 / Accepted: 11 February 2014 / Published: 5 March 2014
Cited by 7 | PDF Full-text (990 KB) | HTML Full-text | XML Full-text
Abstract
The complete genome of human cytomegalovirus (HCMV) was elucidated almost 25 years ago using a traditional cloning and Sanger sequencing approach. Analysis of the genetic content of additional laboratory and clinical isolates has lead to a better, albeit still incomplete, definition of [...] Read more.
The complete genome of human cytomegalovirus (HCMV) was elucidated almost 25 years ago using a traditional cloning and Sanger sequencing approach. Analysis of the genetic content of additional laboratory and clinical isolates has lead to a better, albeit still incomplete, definition of the coding potential and diversity of wild-type HCMV strains. The introduction of a new generation of massively parallel sequencing technologies, collectively called next-generation sequencing, has profoundly increased the throughput and resolution of the genomics field. These increased possibilities are already leading to a better understanding of the circulating diversity of HCMV clinical isolates. The higher resolution of next-generation sequencing provides new opportunities in the study of intrahost viral population structures. Furthermore, deep sequencing enables novel diagnostic applications for sensitive drug resistance mutation detection. RNA-seq applications have changed the picture of the HCMV transcriptome, which resulted in proof of a vast amount of splicing events and alternative transcripts. This review discusses the application of next-generation sequencing technologies, which has provided a clearer picture of the intricate nature of the HCMV genome. The continuing development and application of novel sequencing technologies will further augment our understanding of this ubiquitous, but elusive, herpesvirus. Full article
(This article belongs to the Special Issue Recent CMV Research) Print Edition available
Open AccessReview Incorporation of Hepatitis C Virus E1 and E2 Glycoproteins: The Keystones on a Peculiar Virion
Viruses 2014, 6(3), 1149-1187; doi:10.3390/v6031149
Received: 18 December 2013 / Revised: 21 February 2014 / Accepted: 27 February 2014 / Published: 11 March 2014
Cited by 15 | PDF Full-text (1881 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C virus (HCV) encodes two envelope glycoproteins, E1 and E2. Their structure and mode of fusion remain unknown, and so does the virion architecture. The organization of the HCV envelope shell in particular is subject to discussion as it incorporates or [...] Read more.
Hepatitis C virus (HCV) encodes two envelope glycoproteins, E1 and E2. Their structure and mode of fusion remain unknown, and so does the virion architecture. The organization of the HCV envelope shell in particular is subject to discussion as it incorporates or associates with host-derived lipoproteins, to an extent that the biophysical properties of the virion resemble more very-low-density lipoproteins than of any virus known so far. The recent development of novel cell culture systems for HCV has provided new insights on the assembly of this atypical viral particle. Hence, the extensive E1E2 characterization accomplished for the last two decades in heterologous expression systems can now be brought into the context of a productive HCV infection. This review describes the biogenesis and maturation of HCV envelope glycoproteins, as well as the interplay between viral and host factors required for their incorporation in the viral envelope, in a way that allows efficient entry into target cells and evasion of the host immune response. Full article
(This article belongs to the Special Issue Viral Glycoprotein Incorporation)
Open AccessReview Recent Evidence of Hantavirus Circulation in the American Tropic
Viruses 2014, 6(3), 1274-1293; doi:10.3390/v6031274
Received: 1 October 2013 / Revised: 14 February 2014 / Accepted: 24 February 2014 / Published: 14 March 2014
Cited by 4 | PDF Full-text (512 KB) | HTML Full-text | XML Full-text
Abstract
Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. [...] Read more.
Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview Playing Hide and Seek: How Glycosylation of the Influenza Virus Hemagglutinin Can Modulate the Immune Response to Infection
Viruses 2014, 6(3), 1294-1316; doi:10.3390/v6031294
Received: 23 December 2013 / Revised: 3 March 2014 / Accepted: 7 March 2014 / Published: 14 March 2014
Cited by 35 | PDF Full-text (2458 KB) | HTML Full-text | XML Full-text
Abstract
Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA) glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to [...] Read more.
Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA) glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to shield antigenic sites on HA, thereby promoting virus survival in the face of widespread vaccination and/or infection. However, addition of glycans can also interfere with the receptor binding properties of HA and this must be compensated for by additional mutations, creating a fitness barrier to accumulation of glycosylation sites. In addition, glycans on HA are also recognized by phylogenetically ancient lectins of the innate immune system and the benefit provided by evasion of humoral immunity is balanced by attenuation of infection. Therefore, a fine balance must exist regarding the optimal pattern of HA glycosylation to offset competing pressures associated with recognition by innate defenses, evasion of humoral immunity and maintenance of virus fitness. In this review, we examine HA glycosylation patterns of IAV associated with pandemic and seasonal influenza and discuss recent advancements in our understanding of interactions between IAV glycans and components of innate and adaptive immunity. Full article
(This article belongs to the Section Animal Viruses)
Open AccessReview Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions
Viruses 2014, 6(3), 1317-1335; doi:10.3390/v6031317
Received: 10 January 2014 / Revised: 19 February 2014 / Accepted: 24 February 2014 / Published: 14 March 2014
Cited by 6 | PDF Full-text (715 KB) | HTML Full-text | XML Full-text
Abstract
Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays [...] Read more.
Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. Full article
(This article belongs to the Special Issue Hantaviruses)
Figures

Open AccessReview Super-Resolution Microscopy: A Virus’ Eye View of the Cell
Viruses 2014, 6(3), 1365-1378; doi:10.3390/v6031365
Received: 13 January 2014 / Revised: 1 March 2014 / Accepted: 11 March 2014 / Published: 19 March 2014
Cited by 8 | PDF Full-text (688 KB) | HTML Full-text | XML Full-text
Abstract
It is difficult to observe the molecular choreography between viruses and host cell components, as they exist on a spatial scale beyond the reach of conventional microscopy. However, novel super-resolution microscopy techniques have cast aside technical limitations to reveal a nanoscale view [...] Read more.
It is difficult to observe the molecular choreography between viruses and host cell components, as they exist on a spatial scale beyond the reach of conventional microscopy. However, novel super-resolution microscopy techniques have cast aside technical limitations to reveal a nanoscale view of virus replication and cell biology. This article provides an introduction to super-resolution imaging; in particular, localisation microscopy, and explores the application of such technologies to the study of viruses and tetraspanins, the topic of this special issue. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
Figures

Open AccessReview Role of Virus-Encoded microRNAs in Avian Viral Diseases
Viruses 2014, 6(3), 1379-1394; doi:10.3390/v6031379
Received: 30 December 2013 / Revised: 23 February 2014 / Accepted: 28 February 2014 / Published: 21 March 2014
Cited by 9 | PDF Full-text (1009 KB) | HTML Full-text | XML Full-text
Abstract
With total dependence on the host cell, several viruses have adopted strategies to modulate the host cellular environment, including the modulation of microRNA (miRNA) pathway through virus-encoded miRNAs. Several avian viruses, mostly herpesviruses, have been shown to encode a number of novel [...] Read more.
With total dependence on the host cell, several viruses have adopted strategies to modulate the host cellular environment, including the modulation of microRNA (miRNA) pathway through virus-encoded miRNAs. Several avian viruses, mostly herpesviruses, have been shown to encode a number of novel miRNAs. These include the highly oncogenic Marek’s disease virus-1 (26 miRNAs), avirulent Marek’s disease virus-2 (36 miRNAs), herpesvirus of turkeys (28 miRNAs), infectious laryngotracheitis virus (10 miRNAs), duck enteritis virus (33 miRNAs) and avian leukosis virus (2 miRNAs). Despite the closer antigenic and phylogenetic relationship among some of the herpesviruses, miRNAs encoded by different viruses showed no sequence conservation, although locations of some of the miRNAs were conserved within the repeat regions of the genomes. However, some of the virus-encoded miRNAs showed significant sequence homology with host miRNAs demonstrating their ability to serve as functional orthologs. For example, mdv1-miR-M4-5p, a functional ortholog of gga-miR-155, is critical for the oncogenicity of Marek’s disease virus. Additionally, we also describe the potential association of the recently described avian leukosis virus subgroup J encoded E (XSR) miRNA in the induction of myeloid tumors in certain genetically-distinct chicken lines. In this review, we describe the advances in our understanding on the role of virus-encoded miRNAs in avian diseases. Full article
(This article belongs to the Special Issue Viruses and miRNAs)
Open AccessReview Gene Therapy Targeting HIV Entry
Viruses 2014, 6(3), 1395-1409; doi:10.3390/v6031395
Received: 4 November 2013 / Revised: 19 February 2014 / Accepted: 26 February 2014 / Published: 21 March 2014
Cited by 8 | PDF Full-text (565 KB) | HTML Full-text | XML Full-text
Abstract
Despite the unquestionable success of antiretroviral therapy (ART) in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an [...] Read more.
Despite the unquestionable success of antiretroviral therapy (ART) in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT) using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection. Full article
(This article belongs to the Special Issue Gene Therapy for Retroviral Infections)

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