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Viruses, Volume 5, Issue 6 (June 2013) – 12 articles , Pages 1374-1606

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6837 KiB  
Review
NF-κB and IRF7 Pathway Activation by Epstein-Barr Virus Latent Membrane Protein 1
by Ina Ersing, Katharina Bernhardt and Benjamin E. Gewurz
Viruses 2013, 5(6), 1587-1606; https://doi.org/10.3390/v5061587 - 21 Jun 2013
Cited by 58 | Viewed by 19296
Abstract
The principal Epstein-Barr virus (EBV) oncoprotein, Latent Membrane Protein 1 (LMP1), is expressed in most EBV-associated human malignancies. LMP1 mimics CD40 receptor signaling to provide infected cells with constitutive NF-κB, MAP kinase, IRF7, and PI3 kinase pathway stimulation. EBV-transformed B-cells are particularly dependent [...] Read more.
The principal Epstein-Barr virus (EBV) oncoprotein, Latent Membrane Protein 1 (LMP1), is expressed in most EBV-associated human malignancies. LMP1 mimics CD40 receptor signaling to provide infected cells with constitutive NF-κB, MAP kinase, IRF7, and PI3 kinase pathway stimulation. EBV-transformed B-cells are particularly dependent on constitutive NF-κB activity, and rapidly undergo apoptosis upon NF-κB blockade. Here, we review LMP1 function, with special attention to current understanding of the molecular mechanisms of LMP1-mediated NF-κB and IRF7 pathway activation. Recent advances include the elucidation of transmembrane motifs important for LMP1 trafficking and ligand-independent signaling, analysis of genome-wide LMP1 gene targets, and the identification of novel cell proteins that mediate LMP1 NF-κB and IRF7 pathway activation. Full article
(This article belongs to the Special Issue Recent Progress in EBV Research)
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2056 KiB  
Review
Bromodomain Proteins in HIV Infection
by Daniela Boehm, Ryan J. Conrad and Melanie Ott
Viruses 2013, 5(6), 1571-1586; https://doi.org/10.3390/v5061571 - 21 Jun 2013
Cited by 33 | Viewed by 10717
Abstract
Bromodomains are conserved protein modules of ~110 amino acids that bind acetylated lysine residues in histone and non-histone proteins. Bromodomains are present in many chromatin-associated transcriptional regulators and have been linked to diverse aspects of the HIV life cycle, including transcription and integration. [...] Read more.
Bromodomains are conserved protein modules of ~110 amino acids that bind acetylated lysine residues in histone and non-histone proteins. Bromodomains are present in many chromatin-associated transcriptional regulators and have been linked to diverse aspects of the HIV life cycle, including transcription and integration. Here, we review the role of bromodomain-containing proteins in HIV infection. We begin with a focus on acetylated viral factors, followed by a discussion of structural and biological studies defining the involvement of bromodomain proteins in the HIV life cycle. We end with an overview of promising new studies of bromodomain inhibitory compounds for the treatment of HIV latency. Full article
(This article belongs to the Special Issue Chromatin Control of Viral Infection)
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1968 KiB  
Review
Dendritic Cells in Human Pneumovirus and Metapneumovirus Infections
by Antonieta Guerrero-Plata
Viruses 2013, 5(6), 1553-1570; https://doi.org/10.3390/v5061553 - 20 Jun 2013
Cited by 7 | Viewed by 7347
Abstract
Lung dendritic cells (DC) play a fundamental role in sensing invading pathogens, as well as in the control of tolerogenic responses in the respiratory tract. Their strategic localization at the site of pathogen entry makes them particularly susceptible to initial viral invasion. Human [...] Read more.
Lung dendritic cells (DC) play a fundamental role in sensing invading pathogens, as well as in the control of tolerogenic responses in the respiratory tract. Their strategic localization at the site of pathogen entry makes them particularly susceptible to initial viral invasion. Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) belong to the Paramyxoviridae family, within the Pneumovirus and Metapneumovirus genera, respectively. hRSV and hMPV are significant human respiratory pathogens that cause similar clinical manifestations and affect many of the same subpopulations. However, they differentially activate the host immune response, including DC, which represents a fundamental link between the innate and adaptive immune response. In this review, the role of DC in the immune response against hRSV and hMPV infections, as well as the inhibitory effects of these paramyxoviruses on the DC immunity will be discussed. Full article
(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)
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19770 KiB  
Review
Simian Foamy Virus in Non-Human Primates and Cross-Species Transmission to Humans in Gabon: An Emerging Zoonotic Disease in Central Africa?
by Augustin Mouinga-Ondémé and Mirdad Kazanji
Viruses 2013, 5(6), 1536-1552; https://doi.org/10.3390/v5061536 - 19 Jun 2013
Cited by 24 | Viewed by 9977
Abstract
It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy [...] Read more.
It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy virus (SFV), from primates to humans. To better understand this retroviral “zoonosis” in natural settings, we evaluated the presence of SFV in both captive and wild non-human primates and in humans at high risk, such as hunters and people bitten by a non-human primate, in Gabon, central Africa. A high prevalence of SFV was found in blood samples from non-human primates and in bush meat collected across the country. Mandrills were found to be highly infected with two distinct strains of SFV, depending on their geographical location. Furthermore, samples collected from hunters and non-human primate laboratory workers showed clear, extensive cross-species transmission of SFV. People who had been bitten by mandrills, gorillas and chimpanzees had persistent SFV infection with low genetic drift. Thus, SFV is presumed to be transmitted from non-human primates mainly through severe bites, involving contact between infected saliva and blood. In this review, we summarize and discuss our five-year observations on the prevalence and dissemination of SFV in humans and non-human primates in Gabon. Full article
(This article belongs to the Special Issue Recent Progress in Foamy Virus (FV) Research)
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9069 KiB  
Review
The Role of Bacterial Chaperones in the Circulative Transmission of Plant Viruses by Insect Vectors
by Adi Kliot and Murad Ghanim
Viruses 2013, 5(6), 1516-1535; https://doi.org/10.3390/v5061516 - 19 Jun 2013
Cited by 27 | Viewed by 11114
Abstract
Persistent circulative transmission of plant viruses involves complex interactions between the transmitted virus and its insect vector. Several studies have shown that insect vector proteins are involved in the passage and the transmission of the virus. Interestingly, proteins expressed by bacterial endosymbionts that [...] Read more.
Persistent circulative transmission of plant viruses involves complex interactions between the transmitted virus and its insect vector. Several studies have shown that insect vector proteins are involved in the passage and the transmission of the virus. Interestingly, proteins expressed by bacterial endosymbionts that reside in the insect vector, were also shown to influence the transmission of these viruses. Thus far, the transmission of two plant viruses that belong to different virus genera was shown to be facilitated by a bacterial chaperone protein called GroEL. This protein was shown to be implicated in the transmission of Potato leafroll virus (PLRV) by the green peach aphid Myzus persicae, and the transmission of Tomato yellow leaf curl virus (TYLCV) by the sweetpotato whitefly Bemisia tabaci. These tri-trophic levels of interactions and their possible evolutionary implications are reviewed. Full article
(This article belongs to the Special Issue Plant Viruses)
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653 KiB  
Review
The Role of Chromatin in Adenoviral Vector Function
by Carmen M. Wong, Emily R. McFall, Joseph K. Burns and Robin J. Parks
Viruses 2013, 5(6), 1500-1515; https://doi.org/10.3390/v5061500 - 14 Jun 2013
Cited by 14 | Viewed by 6806
Abstract
Vectors based on adenovirus (Ad) are one of the most commonly utilized platforms for gene delivery to cells in molecular biology studies and in gene therapy applications. Ad is also the most popular vector system in human clinical gene therapy trials, largely due [...] Read more.
Vectors based on adenovirus (Ad) are one of the most commonly utilized platforms for gene delivery to cells in molecular biology studies and in gene therapy applications. Ad is also the most popular vector system in human clinical gene therapy trials, largely due to its advantageous characteristics such as high cloning capacity (up to 36 kb), ability to infect a wide variety of cell types and tissues, and relative safety due to it remaining episomal in transduced cells. The latest generation of Ad vectors, helper‑dependent Ad (hdAd), which are devoid of all viral protein coding sequences, can mediate high-level expression of a transgene for years in a variety of species ranging from rodents to non-human primates. Given the importance of histones and chromatin in modulating gene expression within the host cell, it is not surprising that Ad, a nuclear virus, also utilizes these proteins to protect the genome and modulate virus- or vector‑encoded genes. In this review, we will discuss our current understanding of the contribution of chromatin to Ad vector function. Full article
(This article belongs to the Special Issue Chromatin Control of Viral Infection)
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274 KiB  
Review
Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding
by Stephen N. White and Donald P. Knowles
Viruses 2013, 5(6), 1466-1499; https://doi.org/10.3390/v5061466 - 14 Jun 2013
Cited by 30 | Viewed by 7530
Abstract
Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility [...] Read more.
Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions. Full article
(This article belongs to the Special Issue Small Ruminant Lentiviruses)
5275 KiB  
Review
Exploiting Herpes Simplex Virus Entry for Novel Therapeutics
by Satvik Hadigal and Deepak Shukla
Viruses 2013, 5(6), 1447-1465; https://doi.org/10.3390/v5061447 - 10 Jun 2013
Cited by 25 | Viewed by 8602
Abstract
Herpes Simplex virus (HSV) is associated with a variety of diseases such as genital herpes and numerous ocular diseases. At the global level, high prevalence of individuals who are seropositive for HSV, combined with its inconspicuous infection, remains a cause for major concern. [...] Read more.
Herpes Simplex virus (HSV) is associated with a variety of diseases such as genital herpes and numerous ocular diseases. At the global level, high prevalence of individuals who are seropositive for HSV, combined with its inconspicuous infection, remains a cause for major concern. At the molecular level, HSV entry into a host cell involves multiple steps, primarily the interaction of viral glycoproteins with various cell surface receptors, many of which have alternate substitutes. The molecular complexity of the virus to enter a cell is also enhanced by the existence of different modes of viral entry. The availability of many entry receptors, along with a variety of entry mechanisms, has resulted in a virus that is capable of infecting virtually all cell types. While HSV uses a wide repertoire of viral and host factors in establishing infection, current therapeutics aimed against the virus are not as diversified. In this particular review, we will focus on the initial entry of the virus into the cell, while highlighting potential novel therapeutics that can control this process. Virus entry is a decisive step and effective therapeutics can translate to less virus replication, reduced cell death, and detrimental symptoms. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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158 KiB  
Review
Viral and Host Factors Required for Avian H5N1 Influenza A Virus Replication in Mammalian Cells
by Hong Zhang, Benjamin G. Hale, Ke Xu and Bing Sun
Viruses 2013, 5(6), 1431-1446; https://doi.org/10.3390/v5061431 - 10 Jun 2013
Cited by 26 | Viewed by 8510
Abstract
Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the [...] Read more.
Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the basic viral and cellular mechanisms that contribute to infection of mammalian species with avian influenza viruses is essential for developing prevention and control measures against possible future human pandemics. Multiple physical and functional cellular barriers can restrict influenza A virus infection in a new host species, including the cell membrane, the nuclear envelope, the nuclear environment, and innate antiviral responses. In this review, we summarize current knowledge on viral and host factors required for avian H5N1 influenza A viruses to successfully establish infections in mammalian cells. We focus on the molecular mechanisms underpinning mammalian host restrictions, as well as the adaptive mutations that are necessary for an avian influenza virus to overcome them. It is likely that many more viral and host determinants remain to be discovered, and future research in this area should provide novel and translational insights into the biology of influenza virus-host interactions. Full article
(This article belongs to the Special Issue H5N1 Influenza Virus)
477 KiB  
Article
Influence of Naturally Occurring Simian Foamy Viruses (SFVs) on SIV Disease Progression in the Rhesus Macaque (Macaca mulatta) Model
by Anil Choudhary, Teresa A. Galvin, Dhanya K. Williams, Joel Beren, Mark A. Bryant and Arifa S. Khan
Viruses 2013, 5(6), 1414-1430; https://doi.org/10.3390/v5061414 - 06 Jun 2013
Cited by 27 | Viewed by 7513
Abstract
We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were [...] Read more.
We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIVmac239 virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV−/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6–28 weeks, particularly after reaching plateau at 20–28 weeks, in the CD4+ and CD8+ T-cell numbers over the entire study period (2–43 weeks), and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4+ T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans. Full article
(This article belongs to the Special Issue Recent Progress in Foamy Virus (FV) Research)
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8182 KiB  
Review
Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
by Matthew Reeves and John Sinclair
Viruses 2013, 5(6), 1395-1413; https://doi.org/10.3390/v5061395 - 03 Jun 2013
Cited by 34 | Viewed by 9023
Abstract
Lytic infection of differentiated cell types with human cytomegalovirus (HCMV) results in the temporal expression of between 170–200 open reading frames (ORFs). A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and [...] Read more.
Lytic infection of differentiated cell types with human cytomegalovirus (HCMV) results in the temporal expression of between 170–200 open reading frames (ORFs). A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and cellular mechanisms associated with the co-ordinated recruitment of transcription complexes and, more recently, higher order chromatin structure. Importantly, HCMV, like all herpes viruses, establishes a lifelong latent infection of the host—one major site of latency being the undifferentiated haematopoietic progenitor cells resident in the bone marrow. Crucially, the establishment of latency is concomitant with the recruitment of cellular enzymes that promote extensive methylation of histones bound to the major immediate early promoter. As such, the repressive chromatin structure formed at the major immediate early promoter (MIEP) elicits inhibition of IE gene expression and is a major factor involved in maintenance of HCMV latency. However, it is becoming increasingly clear that a distinct subset of viral genes is also expressed during latency. In this review, we will discuss the mechanisms that control the expression of these latency-associated transcripts and illustrate that regulation of these latency-associated promoters is also subject to chromatin mediated regulation and that the instructive observations previously reported regarding the negative regulation of the MIEP during latency are paralleled in the regulation of latent gene expression. Full article
(This article belongs to the Special Issue Chromatin Control of Viral Infection)
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719 KiB  
Review
Current Understanding of the Role of the Brd4 Protein in the Papillomavirus Lifecycle
by Alison A. McBride and Moon Kyoo Jang
Viruses 2013, 5(6), 1374-1394; https://doi.org/10.3390/v5061374 - 30 May 2013
Cited by 37 | Viewed by 11281
Abstract
The Brd4 protein is an epigenetic reader that is central to regulation of cellular transcription and mitotic bookmarking. The transcription and replication proteins of many viruses interact with Brd4. We describe the multiple roles of Brd4 in the papillomavirus lifecycle. Full article
(This article belongs to the Special Issue Chromatin Control of Viral Infection)
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