Although vzv cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that vzv is latent in ganglia. Although research has progressed rapidly since it was published in 2000, the book surveys the current knowledge of the molecular biology of vzv as well as the. The neurobiology of varicella zoster virus infection. This is a pdf file of an article that has undergone enhancements after acceptance, such as the addition of a cover. Varicella or chickenpox is a common and highly contagious exanthematic disease caused by the varicella zoster virus vzv that during primary infection has the ability to establish latency. Disseminated zoster in an adult patient with extensive. Orf7 is an important virulence determinant of vzv in both human skin and nerve tissues, however, its specific function and involved molecular mechanism in vzv pathogenesis remain largely elusive.
The conserved herpesvirus glycoprotein gb and the heterodimer ghgl mediate virion envelope fusion with cell membranes during virus entry. Following primary infection, vzv establishes latency in the sensory. Viruses free fulltext molecular aspects of varicellazoster virus. Like other herpesviruses, vzv persists in the body as a latent infection after the primary first infection. Varisela merupakan manifestasi dari infeksi virus varicella zoster primer yang. Varicella zoster virus causes two distinct clinical conditions. Primary varicella infection chickenpox was not reliably distinguished from smallpox until the end of the 19th century. To determine whether vzv virions remained cell associated or. Molecular mechanisms of varicella zoster virus pathogenesis varicella zoster virus vzv is the causative agent of varicella chickenpox and zoster shingles. Such tropisms are essential both for primary infection, which manifests itself as chickenpox varicella, and subsequent reactivation to cause herpes zoster shingles. Jun 12, 2012 human alphaherpesviruses including herpes simplex viruses hsv1, hsv2 and varicella zoster virus vzv establish persistent latent infection in sensory neurons for the life of the host. Epidemiology of varicella zoster virus varicella zoster virus causes two distinct clinical conditions. Nowadays effective treatment is available and a vaccine has been developed and licensed. Review open access herpes simplex virus and varicella.
Manipulation of the innate immune response by varicella. Varicella zoster virus varicella zoster virus vzv is a member of the alpha subfamily of herpesviruses and is responsible for the human diseases of the chicken pox and shingles. Infection with varicella zoster virus vzv causes varicella chickenpox, which can be severe in immunocompromised individuals, infants and adults. Frontiers varicella virushost interactions during latency. Figure 2 from varicella zoster virus infection semantic scholar. Although no animal model yet reproduces all aspects of vzv infection, recently developed models of vzv infection, and the creation of genetically altered vzv recombinants, are yielding new information about primary viraemia and latency. The schematic illustrates viral factors that ensure spread to the skin surface after varicella zoster virus vzv is delivered to cutaneous sites of replication by infected tcells or by retrograde axonal transport from neurons lefthand side.
The mechanisms of hsv and vzv latency are also different, and this. While the molecular triggers of vzv reactivation are not well understood, there. May 12, 2015 varicella zoster virus vzv, of the family alphaherpesvirinae, causes varicella in children and young adults, potentially leading to herpes zoster later in life on reactivation from latency. Inadditionto its tropism for skin and neural cells, vzv infects t cells, which provides a mechanism for viral transport to the skin 2, 3. Equine herpesvirus type 1 ehv1 is an alphaherpesvirus related to pseudorabies virus prv and varicella zoster virus vzv. A novel mutation of varicellazoster virus associated to fatal. Molecular mechanisms of varicella zoster virus pathogenesis figure 3 vzv skin tropism. Varicella zoster virus vzv is an exclusively human highly neurotropic alphaherpesvirus.
The virus exhibits multiple cell tropisms, infecting peripheral blood mononuclear cells and skin cells before establishing latency in sensory neurons. Viruses such as varicella zoster chickenpox and herpesviridae herpes simplex viruses, varicella zoster virus, cytomegalovirus etc can hide from the immune system in neurons and nonneuronal cells where they may persist for many years, before emerging. This book is the most comprehensive publication on varicella zoster virus vzv to date. Varicellazoster virus pathogenesis and immunobiology.
Varicellazoster virus vzv, a member of the herpesvirus family, is known as the causative agent of chickenpox varicella and shingles zoster. Varicella centers for disease control and prevention. The term shingles derives from the medieval latin word cingulus, a girdle. Varicella zoster virus vzv is the etiologic agent of varicella chickenpox and herpes zoster shingles and causes characteristic cutaneous lesions in both diseases. Frontiers the pathogenesis and immune evasive mechanisms of. However, the use of human tissue xenografts in mice with severe combined immunodeficiency scid enables the analysis of vzv infection in differentiated human cells in their typical tissue microenvironment.
Methods three thousand fourteen children were recruited from chinese kindergarten students aged from. Pemanfaatan eritropoietin sebagai neuroprotektan terhadap. This lifelong relationship continually subjects vzv to the host immune system and as. Sen n, mukherjee g and arvin am 2020 the use of single cell mass cytometry to define the molecular mechanisms of varicella zoster virus lymphotropism. Epigenetics of human herpesvirus latency wikipedia. Herpes zoster results from reactivation of endogenous varicellazoster virus.
Primary infection usually causes chickenpox varicella, after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. The primary varicella zoster virus vzv infection results in chickenpox varicella, which is transmitted via the airborne route. Reactivation of the virus leads to virus replication, which causes zoster shingles in tissues innervated by the involved neurons, inflammation and cell death a process that can lead to. C, with a cterminal truncation of orf47, and roka47dn, with a point mutation in the conserved kinase motif, showed that orf47 kinase function was necessary for optimal vzv replication in human skin xenografts in scid. It is a specialized field of study in virology pathogenesis is a qualitative description of the process by which an initial infection causes disease. Review open access herpes simplex virus and varicella zoster virus, the house guests who never leave paul r kinchington1,2, anthony j st leger1,3, jeanmarc g guedon1,2 and robert l hendricks1,2,3 abstract human alphaherpesviruses including herpes simplex viruses hsv1, hsv2 and varicella zoster virus vzv establish. During this period, no virus particles are produced and no obvious neuronal damage occurs. Alphaherpesvirus, herpes simplex virus, hsv, varicella zoster virus, vzv, immunity, pathogenesis introduction herpes simplex viruses hsv1, hsv2 and varicella zoster virus vzv are related human alphaherpesviruses that cause common, selfresolving diseases of the. Differential requirement for cell fusion and virion formation in the pathogenesis of varicella zoster virus infection in skin and t cells jaya besser, 1 minako ikoma, 2 konstanze fabel, 3 marvin h. Varicella 353 22 varicella is an acute infectious disease caused by varicella zoster virus vzv. Latency in vitro of varicellazoster virus in cells derived. Herpes simplex viruses hsv 1 and 2 and varicellazoster. Cohen 5 pathogenesis of primary infection 105 charles grose, ming ye, and jorge padilla 6 pathogenesis of latency and.
Signaltransducerandactivatoroftranscription3stat3 and. Viral pathogenesis is the study of the process and mechanisms by which viruses cause diseases in their target hosts, often at the cellular or molecular level. The natural history of varicella zoster virus vzv infection and the molecular mechanisms of viral pathogenesis are incompletely understood. However, the use of human tissue xenografts in mice with severe combined immunodeficiency scid enables the analysis of vzv infection in. We performed the current study to explore the seroprevalence of vzv infection in chinese children in order to provide more information for improvement of varicella vaccination in china. Varicella zoster virus vzv is a neurotropic alphaherpesvirus and the causative agent of varicella chickenpox in humans. An unusual distribution of herpes zoster mandibularis post total.
Human alphaherpesvirus 3 hhv3, usually referred to as the varicellazoster virus vzv, is one of nine herpesviruses known to infect humans. Part ii molecular biology and pathogenesis 2 molecular evolution of alphaherpesviruses 25 andrew j. Molecular mechanisms of varicella zoster virus pathogenesis. Jul 19, 2019 background varicella zoster virus vzv infection in children is an important public health problem in china.
Varicella zoster virus vzv infection provides a valuable model for investigating cellcell fusion because of the importance of this process for pathogenesis in human skin and sensory ganglia. Vzv is highly infectious, but in the usa the incidence of varicella has been reduced by 7687% as a result of the varicella vaccine. Viruses are able to initiate infection, disperse through. Primary vzv infection causes varicella chickenpox, a contagious rash illness typically occurring among children. Pdf molecular mechanisms of varicella zoster virus pathogenesis. Frontiers the use of single cell mass cytometry to. Igm antibody detection can assist with acute diagnosis. Molecular and therapeutic aspects of varicellazoster virus. Seroprevalence and molecular characteristics of varicella. Varicella zoster virus vzv is a neurotropic alpha herpes virus and the causative agent of varicella.
Vzv pathogenesis depends on reprogramming cell signalling pathways within infected cells to support cell survival and disrupt innate antiviral. However, few studies have investigated the role of pml nbs in viral pathogenesis or mechanisms by which they are modified during viral infection in vivo. Varicella zoster virus vzv was once thought to be a fairly innocuous. The messaoudi lab at uci is looking to fill 2 postdoctoral scholar positions. What is the pathophysiology of varicellazoster virus vzv. Varicella zoster virus vzv, of the family alphaherpesvirinae, causes varicella in children and young adults, potentially leading to herpes zoster later in life on reactivation from latency. These mutant viruses grow more rapidly in cell grose c, tyler s, peters g, hiebert j, stephens gm, ruyeshan wt, et culture than the wild type grose et. The evolutionary value of this process to vzv is likely to be that the mechanism prevents highly. Dissociated human dorsal root ganglion cultures were infected with vzv and maintained for 1 wk in the. Natural killer cells restrict vzv replication by secreting antiviral molecules ifn. Herpes zoster can afflict the elderly with a debilitating condition, postherpetic neuralgia, triggering severe, untreatable pain for. Functionsoftheuniquenterminalregionofglycoproteine in the. The taatgaratlike elements on the ie62 promoter bind to vzv orf10 protein, oct, and hcf1.
Sommer, 1 leigh zerboni, 1 charles grose, 2 and ann m. Pdf molecular mechanisms of varicella zoster virus. Simian varicella virus svv infection of nonhuman primates is a useful animal model of vzv pathogenesis in humans mahalingam et al. Investigating vzv pathogenesis is challenging as vzv is a. Virology and clinical management is published in association with the vzv research foundation. Primary vzv infection likely occurs through inhalation of virus either in respiratory droplets 1, 2 or from shedding varicella lesions 3 or through direct contact with infectious vesicular. This schematic illustrates active infection of dorsal root ganglia drg which is characterized by the transcription of genes for example, genes encoding glycoprotein b gb, immediate early protein 62 ie62 and ie63 that produce proteins that are required for lytic infection, varicella zoster virus vzv genome synthesis, virus assembly in neurons and satellite cells, release of vzv into intracellular spaces and fusion of some neurons and satellite cells27 left panel. Primary varicella zoster virus infection results in chickenpox varicella, which may result in complications. However, cellfree vzv is detectable in vesicular fluid from varicella and herpes zoster skin lesions as well as in infected human skin xenografts in scidhu mice. Varicella zoster virus vzv is a neurotropic herpesvirus that infects nearly all humans. Robust proinflammatory and lesser antiinflammatory immune. Varicellazoster virus orf7 interacts with orf53 and plays. Following primary infection, vzv establishes latency in the sensory ganglia from which it can reactivate resulting in herpes zoster, a potentially debilitating disease that affects the elderly and immune compromised individuals.
Alphaherpes viruses can induce apoptosis, autophagy and necrosis through different molecular mechanisms. The virus establishes latency in the dorsal root ganglia during varicella and, when reactivated, travels along the sensory nerve axons to cause shingles herpes zoster hz. Varicella zoster virus vzv encodes three immediateearly proteins, ie4, ie62, and ie63. A site of varicellazoster virus vulnerability identified by. Topics covered include viral replication, latency, immune mechanisms, epidemiology and disease manifestations. Frontiers the pathogenesis and immune evasive mechanisms. Investigating the molecular mechanisms of vzv pathogenesis has been difficult because of vzvs restricted. Herpes zoster pathogenesis and cellmediated immunity and. To shed further light on the role of the gbghgl fusion complex in vzv pathogenesis. Regardless of the homology between the different virus strains, the three viruses are characterized by varying pathologies.
Varicella zoster virus dna at inoculation sites and in saliva after zostavax immunization. Varicella zoster virus is sensed via unknown mechanisms by. Vzv remains highly cell associated and is not released during productive infection of cultured cells, such as hfs, and explanted skin tissue infected in vitro 25, 27. It causes chickenpox varicella, a disease most commonly affecting children, teens, and young adults, and shingles herpes zoster in adults. Review open access herpes simplex virus and varicella zoster. Nature of the varicella zoster agent that varicella is caused by an infectious agent was demonstrated in 1875 by steiner. Investigating vzv pathogenesis is challenging as vzv is a humanspecific virus and infection does not occur, or is highly restricted, in other species. The structure of the fusion glycoprotein of newcastle disease virus suggests a novel paradigm for the molecular mechanism of membrane fusion.
Varicellazoster virus in cerebrospinal fluid at relapses of. These viruses have their lytic phase in mucoepithelial cells and are latent in neuronal cells. Immune evasion as a pathogenic mechanism of varicella zoster. For example, this model provides a means to rapidly perplexing state. Pcr amplification andor nucleic acid probes to detect viral nucleic acid in body fluids or tissues. In the past decades, considerable knowledge about the transmission as well as the clinical and epidemiological aspects of vzv infection has been accumulated. Vzv infections are speciesspecific to humans, but can survive in external. Viral disease is the sum of the effects of viral replication on the host and the hosts subsequent immune response against the virus. Following primary infection, vzv establishes latency in the sensory ganglia and can reactivate to cause herpes zoster, more commonly known as shingles, which causes significant morbidity, and on rare occasions mortality, in the elderly. Jan 24, 2020 varicella zoster virus vzv is the causative agent of chickenpox varicella and shingles herpes zoster.
Although research has progressed rapidly since it was published in 2000, the book surveys the current knowledge of the. Ehv1 is responsible for respiratory disorders, abortion, neonatal foal death and equine herpes myeloencephalopathy ehm. The mechanisms by which the immune system regulates latency and reactivation after varicella zoster virus vzv infection in humans are unknown. The use of single cell mass cytometry to define the molecular. Latent infection can reactivate resulting in herpes zoster shingles. Mechanisms of varicella pathogenesis messaoudi lab.
Productive varicellazoster virus infection of cultured. Varicella zoster virus vzv is a neurotropic alpha herpes virus and the causative. All three viruses have the potential to reactivate causing recurrent disease. Varicella zoster virus productively infects human natural killer cells. Varicellazoster virus orf7 interacts with orf53 and plays a. Herpes simplex virus and varicella zoster virus, the house. To date, vzv has been shown to induce apoptosis, primarily through the intrinsic pathway in different cell types, except for neurons in which the virus becomes latent. This virus is one of the major pathogens affecting horses worldwide.
Feb 01, 2015 varicella zoster virus vzv, a neurotropic alphaherpesvirus, is the etiologic agent of varicella chickenpox and herpes zoster hz, shingles. Varicellazoster virus vzv human alphaherpesvirus 3 hhv3, usually referred to as the varicellazoster virus vzv, is one of nine herpesviruses known to infect humans. Varicella zoster virus vzv is a member of the alpha subfamily of herpesviruses and is responsible for the human diseases of the chicken pox and shingles. Primary varicellazoster virus vzv infection causes varicella chickenpox and the establishment of a lifelong latent infection in ganglionic neurons. Investigating vzv pathogenesis is challenging as vzv is a humanspecific virus and infection. Pathogenesis and current approaches to control of varicellazoster. Pathogenesis is a qualitative description of the process by which an initial infection causes disease. Varicella zoster virus vzv is a dna virus and is a member of the herpesvirus group. Abortive intrabronchial infection of rhesus macaques with. In the 1421 days incubation period, vzv replication in the skin is partly. Human alphaherpesvirus 3 hhv3, usually referred to as the varicellazoster virus vzv. Vzv and other members of the herpesvirus family are distinguished by their ability to establish a latent infection, with the potential to reactivate and spread virus to other susceptible individuals. We are looking for motivated and collaborative postdoctoral associates interested in.
Previous surgery can disrupt mechanisms of varicella zoster virus reactivation. A cycle of molecular adsorbent recirculating system mars w. Years after the initial infection, vzv can reactivate to cause herpes zoster shingles, normally presenting as. Varicella zoster virus vzv is a human alphaherpesvirus that causes varicella as the primary infection, and zoster upon reactivationfromlatency inthesensoryganglia1. Primary infection is followed by latency in ganglionic neurons. Does apoptosis play a role in varicella zoster virus. Varicella zoster virus vzv is the causative agent of varicella chickenpox and zoster shingles. Over the last decade, ehv1 has received growing attention due to the. Feb 10, 2014 varicella zoster virus vzv is the causative agent of varicella chickenpox and zoster shingles. Immunobiology of varicellazoster virus infection the journal of. Vzv reactivation, even decades after primary infection, causes herpes zoster. The protein product of varicella zoster virus vzv orf47 is a serinethreonine protein kinase and tegument component.
Varicella zoster virus vzv is a neurotropic alphaherpesvirus that causes chickenpox and shingles. Molecular and therapeutic aspects of varicellazoster. The successful development of a vaccine reflects intense research interest in this virus over recent years, and this book surveys current knowledge of the molecular biology, pathogenesis and clinical features of vzv as the causative agent of chickenpox and zoster shingles. Evaluation of two recombinants of the oka strain, roka47. Advances in the understanding of the pathogenesis and. In 1875, rudolf steiner demonstrated that chickenpox was caused by an infectious agent by inoculating. Pdf varicella zoster virus vzv is the causative agent of varicella chickenpox and zoster shingles. Disruption of pml nuclear bodies is mediated by orf61 sumo. A potential in vitro model of varicella zoster virus vzv latency was developed. Differential requirement for cell fusion and virion formation. In 1875, rudolf steiner demonstrated that chickenpox.
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