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Special Issue "Antiviral Responses to Herpes Viruses"

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Antivirals & Vaccines".

Deadline for manuscript submissions: closed (15 August 2009)

Special Issue Editor

Guest Editor
Prof. Dr. Philippe Georgel

Laboratoire d'ImmunoGénétique Moléculaire Humaine, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, 4 rue Kirschleger, 67085 Strasbourg, Cedex, France
Fax: +33 390 244 016
Interests: VSV; MCMV; TLR; nuclear receptors; interferon; innate immunity

Special Issue Information

Dear Colleagues,

Herpes viruses are usually ubiquitous pathogens which are responsible for only asymptomatic or benign infections in immunocompetent hosts. However, such pathogens may also induce dramatic outcome in fragile, immunocompromised recipients such as transplanted patients. Recently, this family of viruses has been the subject of intense attention because their large DNA genome has been shown to encode microRNAs whose functions are now intensely debated. These non-coding small RNAs , which are considered major regulators of gene expression, represent a novel type of pathogenicity factor which may explain some of the characteristics of Herpesviridae, such as the establishment of latency and their transformation potential.
This special issue of “viruses” will focus on several aspects of Herpes viruses. Some articles will focus on the immune defense elicited in humans or mice to eradicate natural or experimental infections, whereas others will report investigations of escape mechanisms selected by pathogens to avoid innate or adaptive antiviral strategies. Finally, papers describing approaches designed to identify genes of both the host and the pathogen will illuminate the power of genetic studies to unravel their complex interactions. We expect this combination of complementary studies will translate into novel tools for future vaccine and therapeutic developments.

Prof. Dr. Philippe Georgel
Guest Editor

Keywords

  • Micro RNA
  • latency
  • opportunistic infection
  • cancer
  • transplantation

Published Papers (12 papers)

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Review

Open AccessReview Herpesviruses and Autophagy: Catch Me If You Can!
Viruses 2010, 2(1), 314-333; doi:10.3390/v2010314
Received: 18 November 2009 / Revised: 19 January 2010 / Accepted: 22 January 2010 / Published: 26 January 2010
Cited by 20 | PDF Full-text (1056 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as [...] Read more.
Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. It also acts as a cellular defense mechanism against microorganisms by contributing to both the innate and adaptive immunity, and by eliminating intracellular pathogens (xenophagy). There is growing evidence that host cells try to control Herpesvirus infections by activating the autophagic machinery. However, it is well-known that Herpesviruses are smart pathogens and several, such as HSV-1, HCMV and HHV-8, are known to have developed numerous defense strategies for evading the host’s immune response. Inhibition of the antiviral autophagic mechanism has also been reported. Autophagy has also been shown to enhance the major histocompatibility complex presentation of at least two viral proteins, the EBVencoded EBNA-1 and the HSV-1 encoded gB. In this review, we present an overview of recent advances in our understanding of the complex interplay between autophagy and Herpesviruses. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Interplay between Herpesvirus Infection and Host Defense by PML Nuclear Bodies
Viruses 2009, 1(3), 1240-1264; doi:10.3390/v1031240
Received: 18 November 2009 / Revised: 10 December 2009 / Accepted: 14 December 2009 / Published: 15 December 2009
Cited by 33 | PDF Full-text (197 KB) | HTML Full-text | XML Full-text
Abstract
In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral [...] Read more.
In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication at different stages. The antiviral function of ND10, however, is antagonized by viral regulatory proteins (e.g., ICP0 of herpes simplex virus; IE1 of human cytomegalovirus) which induce either a modification or disruption of ND10. This review will summarize the current knowledge on how viral replication is inhibited by ND10 proteins. Furthermore, herpesviral strategies to defeat this host defense mechanism are discussed. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Cellular Players in the Herpes Simplex Virus Dependent Apoptosis Balancing Act
Viruses 2009, 1(3), 965-978; doi:10.3390/v1030965
Received: 30 September 2009 / Revised: 16 November 2009 / Accepted: 17 November 2009 / Published: 18 November 2009
Cited by 7 | PDF Full-text (239 KB) | HTML Full-text | XML Full-text
Abstract
Apoptosis is triggered as an intrinsic defense against numerous viral infections. Almost every virus encodes apoptotic modulators, and the herpes simplex viruses (HSV) are no exception. During HSV infection, there is an intricate balance between pro- and anti-apoptotic factors that delays apoptotic [...] Read more.
Apoptosis is triggered as an intrinsic defense against numerous viral infections. Almost every virus encodes apoptotic modulators, and the herpes simplex viruses (HSV) are no exception. During HSV infection, there is an intricate balance between pro- and anti-apoptotic factors that delays apoptotic death until the virus has replicated. Perturbations in the apoptotic balance can cause premature cell death and have the potential to dramatically alter the outcome of infection. Recently, certain cellular genes have been shown to regulate sensitivity to HSV-dependent apoptosis. This review summarizes current knowledge of the cellular genes that impact the apoptotic balance during HSV infection. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Figures

Open AccessReview Therapeutic Approaches Using Host Defence Peptides to Tackle Herpes Virus Infections
Viruses 2009, 1(3), 939-964; doi:10.3390/v1030939
Received: 24 July 2009 / Revised: 11 October 2009 / Accepted: 16 November 2009 / Published: 18 November 2009
Cited by 10 | PDF Full-text (593 KB) | HTML Full-text | XML Full-text
Abstract
One of the most common viral infections in humans is caused by herpes simplex virus (HSV). It can easily be treated with nucleoside analogues (e.g., acyclovir), but resistant strains are on the rise. Naturally occurring antimicrobial peptides have been demonstrated to possess [...] Read more.
One of the most common viral infections in humans is caused by herpes simplex virus (HSV). It can easily be treated with nucleoside analogues (e.g., acyclovir), but resistant strains are on the rise. Naturally occurring antimicrobial peptides have been demonstrated to possess antiviral activity against HSV. New evidence has also indicated that these host defence peptides are able to selectively stimulate the innate immune system to fight of infections. This review will focus on the anti-HSV activity of such peptides (both natural and synthetic), describe their mode of action and their clinical potential. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Innate and Adaptive Immune Responses to Herpes Simplex Virus
Viruses 2009, 1(3), 979-1002; doi:10.3390/v1030979
Received: 30 July 2009 / Revised: 13 November 2009 / Accepted: 16 November 2009 / Published: 18 November 2009
Cited by 31 | PDF Full-text (197 KB) | HTML Full-text | XML Full-text
Abstract
Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized [...] Read more.
Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized in vitro and in vivo. Cell types such as NK cells and pDCs contribute to innate anti-HSV responses in vivo. Finally, the adaptive response includes both humoral and cellular components that play important roles in antiviral control and latency. This review summarizes the innate and adaptive effectors that contribute to susceptibility, immune control and pathogenesis of HSV, and highlights the delicate interplay between these two important arms of immunity. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Figures

Open AccessReview The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses
Viruses 2009, 1(3), 760-779; doi:10.3390/v1030760
Received: 18 August 2009 / Revised: 4 November 2009 / Accepted: 5 November 2009 / Published: 5 November 2009
Cited by 8 | PDF Full-text (144 KB) | HTML Full-text | XML Full-text
Abstract
The major immediate-early (IE) gene of human cytomegalovirus (CMV) is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, [...] Read more.
The major immediate-early (IE) gene of human cytomegalovirus (CMV) is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Spontaneous and Engineered Compensatory HSV Mutants that Counteract the Host Antiviral PKR Response
Viruses 2009, 1(3), 510-522; doi:10.3390/v1030510
Received: 24 August 2009 / Revised: 22 October 2009 / Accepted: 22 October 2009 / Published: 22 October 2009
Cited by 4 | PDF Full-text (678 KB) | HTML Full-text | XML Full-text
Abstract
A virulent recombinant HSV lacking the diploid γ134.5 gene (Δγ134.5) have been investigated over the last two decades both for anti-tumor therapy and as vaccine vectors. The first generation vectors, while safe, are incapable of sustained replication in [...] Read more.
A virulent recombinant HSV lacking the diploid γ134.5 gene (Δγ134.5) have been investigated over the last two decades both for anti-tumor therapy and as vaccine vectors. The first generation vectors, while safe, are incapable of sustained replication in the majority of treated patients. An interferon inducible host antiviral kinase, protein kinase R (PKR), limits late viral protein synthesis and replication of Δγ134.5 viruses. This review describes the development of new Δγ134.5 vectors, through serial passage selection and direct viral genome engineering, which demonstrate selective PKR evasion in targeted cells and improved viral replication without restoring neurovirulence. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Identification of Mouse Cytomegalovirus Resistance Loci by ENU Mutagenesis
Viruses 2009, 1(3), 460-483; doi:10.3390/v1030460
Received: 13 August 2009 / Revised: 19 October 2009 / Accepted: 20 October 2009 / Published: 20 October 2009
Cited by 1 | PDF Full-text (284 KB) | HTML Full-text | XML Full-text
Abstract
Host resistance to infection depends on the efficiency with which innate immune responses keep the infectious agent in check. Innate immunity encompasses components with sensing, signaling and effector properties. These elements with nonredundant functions are encoded by a set of host genes, [...] Read more.
Host resistance to infection depends on the efficiency with which innate immune responses keep the infectious agent in check. Innate immunity encompasses components with sensing, signaling and effector properties. These elements with nonredundant functions are encoded by a set of host genes, the resistome. Here, we review our findings concerning the resistome. We have screened randomly mutagenized mice for susceptibility to a natural opportunistic pathogen, the mouse cytomegalovirus. We found that some genes with initially no obvious functions in innate immunity may be critical for host survival to infections, falling into a newly defined category of genes of the resistome. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Dominant-Negative Proteins in Herpesviruses – From Assigning Gene Function to Intracellular Immunization
Viruses 2009, 1(3), 420-440; doi:10.3390/v1030420
Received: 18 August 2009 / Revised: 19 October 2009 / Accepted: 19 October 2009 / Published: 19 October 2009
Cited by 4 | PDF Full-text (572 KB) | HTML Full-text | XML Full-text
Abstract
Investigating and assigning gene functions of herpesviruses is a process, which profits from consistent technical innovation. Cloning of bacterial artificial chromosomes encoding herpesvirus genomes permits nearly unlimited possibilities in the construction of genetically modified viruses. Targeted or randomized screening approaches allow rapid [...] Read more.
Investigating and assigning gene functions of herpesviruses is a process, which profits from consistent technical innovation. Cloning of bacterial artificial chromosomes encoding herpesvirus genomes permits nearly unlimited possibilities in the construction of genetically modified viruses. Targeted or randomized screening approaches allow rapid identification of essential viral proteins. Nevertheless, mapping of essential genes reveals only limited insight into function. The usage of dominant-negative (DN) proteins has been the tool of choice to dissect functions of proteins during the viral life cycle. DN proteins also facilitate the analysis of host-virus interactions. Finally, DNs serve as starting-point for design of new antiviral strategies. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections
Viruses 2009, 1(3), 383-419; doi:10.3390/v1030383
Received: 10 August 2009 / Revised: 1 October 2009 / Accepted: 8 October 2009 / Published: 14 October 2009
Cited by 11 | PDF Full-text (431 KB) | HTML Full-text | XML Full-text
Abstract
Type-I interferons (IFN-I) are cytokines essential for vertebrate antiviral defense, including against herpesviruses. IFN-I have potent direct antiviral activities and also mediate a multiplicity of immunoregulatory functions, which can either promote or dampen antiviral adaptive immune responses. Plasmacytoid dendritic cells (pDCs) are [...] Read more.
Type-I interferons (IFN-I) are cytokines essential for vertebrate antiviral defense, including against herpesviruses. IFN-I have potent direct antiviral activities and also mediate a multiplicity of immunoregulatory functions, which can either promote or dampen antiviral adaptive immune responses. Plasmacytoid dendritic cells (pDCs) are the professional producers of IFN-I in response to many viruses, including all of the herpesviruses tested. There is strong evidence that pDCs could play a major role in the initial orchestration of both innate and adaptive antiviral immune responses. Depending on their activation pattern, pDC responses may be either protective or detrimental to the host. Here, we summarize and discuss current knowledge regarding pDC implication in the physiopathology of mouse and human herpesvirus infections, and we discuss how pDC functions could be manipulated in immunotherapeutic settings to promote health over disease. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview The Natural Selection of Herpesviruses and Virus-Specific NK Cell Receptors
Viruses 2009, 1(3), 362-382; doi:10.3390/v1030362
Received: 14 August 2009 / Revised: 13 October 2009 / Accepted: 13 October 2009 / Published: 13 October 2009
Cited by 24 | PDF Full-text (1017 KB) | HTML Full-text | XML Full-text
Abstract
During the co-evolution of cytomegalovirus (CMV) and natural killer (NK) cells, each has evolved specific tactics in an attempt to prevail. CMV has evolved multiple immune evasion mechanisms to avoid detection by NK cells and other immune cells, leading to chronic infection. [...] Read more.
During the co-evolution of cytomegalovirus (CMV) and natural killer (NK) cells, each has evolved specific tactics in an attempt to prevail. CMV has evolved multiple immune evasion mechanisms to avoid detection by NK cells and other immune cells, leading to chronic infection. Meanwhile, the host has evolved virus-specific receptors to counter these evasion strategies. The natural selection of viral genes and host receptors allows us to observe a unique molecular example of "survival of the fittest", as virus and immune cells try to out-maneuver one another or for the virus to achieve détente for optimal dissemination in the population. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
Open AccessReview Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0)
Viruses 2009, 1(2), 255-275; doi:10.3390/v1020255
Received: 15 July 2009 / Revised: 24 August 2009 / Accepted: 2 September 2009 / Published: 7 September 2009
Cited by 23 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription [...] Read more.
Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single amino acid change in a well conserved cysteine residue of the C3HC4 zinc RING finger of bICP0 grows poorly in cultured cells, and does not reactivate from latency in cattle confirming that the C3HC4 zinc RING finger is crucial for viral growth and pathogenesis. A bICP0 deletion mutant does not induce plaques in permissive cells, but induces autophagy in a cell type dependent manner. In summary, the ability of bICP0 to stimulate productive infection, and repress IFN dependent transcription plays a crucial role in the BoHV-1 infection cycle. Full article
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

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