Chicken pox virus capsid

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CAS Google Scholar. Emsley, P. Features and development of Coot. Acta Crystallogr. Adams, P. Chen, V. MolProbity: all-atom structure validation for macromolecular crystallography. Download references. Changchun Keygen Biological Products Co.

You can also search for this author in PubMed Google Scholar. All authors participated in discussions and paper editing. Peer review information Nature Communications thanks the anonymous reviewers for their contributions to the peer review of this work.

Peer review reports are available. Reprints and Permissions. Sun, J. Cryo-EM structure of the varicella-zoster virus A-capsid. Nat Commun 11, Download citation. Received : 20 July Accepted : 26 August Published : 22 September Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Advanced search. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. Download PDF. Subjects Cryoelectron microscopy Herpes virus Virus structures. Abstract Varicella-zoster virus VZV , a member of the Alphaherpesvirinae subfamily, causes severe diseases in humans of all ages.

Introduction Varicella-zoster virus VZV can establish lifelong persistent infections and cause severe diseases in humans of all ages 1 , 2 , 3. Full size image. Discussion Given that the viral capsid plays a central role in herpesvirus infection and replication, elucidating the structural composition and assembly mechanism of the large capsid is essential for aiding the development of antivirals. Reporting summary Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability The data that support this work is available from the corresponding authors upon reasonable request. References 1. PubMed Article Google Scholar 3. Google Scholar 5. CAS Google Scholar View author publications.

Ethics declarations Competing interests The authors declare no competing interests. Additional information Peer review information Nature Communications thanks the anonymous reviewers for their contributions to the peer review of this work.

Supplementary information. Supplementary Information. Live attenuated VZV vaccines are effective in healthy individuals but are not safe for immunocompromised patients, in whom they cause viraemia, and they can establish latency and reactivate in healthy and in immunodeficient individuals 4 — 6 , , , which is consistent with the lack of attenuation that is observed in T cell and DRG xenografts.

The genetic basis of their attenuation is not defined 58 , The SCID mouse model can be exploited for rational VZV vaccine design by incorporating mutations that dampen replication in skin into the viral genome, similarly to the current vaccine, and, in contrast to the current vaccine, that also interfere with the capacity to infect T cells or to persist in neurons. Antiviral drugs, such as acyclovir and related agents, substantially reduce the risk of severe or fatal VZV infection in immunocompromised patients but have little or no effect on postherpetic neuralgia following zoster in the elderly Knowledge about functional motifs of VZV proteins and how the virus reprogrammes differentiated human cells in vivo might help in designing small-molecule inhibitors with antiviral activity that would also decrease postherpetic neuralgia.

Understanding the principles of VZV pathogenesis at the molecular level has the potential to yield new approaches to prevent and treat VZV infections. The authors thank M. Sommer, X. Che, L. Wang and M. Reichelt, past postdoctoral fellows and students and collaborators and many dedicated colleagues in the field of VZV research for their invaluable contributions. Moffat initiated the development of the SCID mouse model as a postdoctoral fellow in the Arvin laboratory.

Competing interests statement. National Center for Biotechnology Information , U. Nat Rev Microbiol. Author manuscript; available in PMC Jun Oliver , and Ann M. Author information Copyright and License information Disclaimer. Correspondence to: A. Copyright notice. The publisher's final edited version of this article is available at Nat Rev Microbiol. See other articles in PMC that cite the published article. Abstract Varicella zoster virus VZV is the causative agent of varicella chickenpox and zoster shingles.

Open in a separate window. Figure 1. Box 1 VZV genome and virion structure. Box 2 Modelling the pathogenesis of varicella zoster virus infection. Figure 2. VZV T cell tropism According to the model of varicella zoster virus VZV cell-associated viraemia, tonsil T cells are infected following VZV inoculation and replication in respiratory mucosal epithelial cells.

Cellular transcription factors as determinants of T cell tropism Investigating VZV mutants that have disrupted binding sites for cellular transcription factors shows the importance of the synergistic regulation of viral genes by IE62 and cellular cofactors.

Skin tropism Innate cellular responses regulate skin pathogenesis. Figure 3. VZV skin tropism 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 T cells or by retrograde axonal transport from neurons left-hand side.

VZV manipulation of cellular responses VZV suppresses innate responses to produce a virus-filled lesion at the skin surface, where infected keratinocytes release newly-assembled virions 60 FIG.

Promyelocytic leukemia protein PML in the regulation of skin infection PML is a multifunctional protein that has antiviral effects against many viruses and is upregulated by IFNs. Cell—cell fusion and skin tropism Cell—cell fusion is not strictly required for VZV spread, as virions that are released from infected cells can enter adjacent cells Glycoproteins gE and gI as determinants of skin infection Although VZV isolates can be classified into several distinct clades that reflect their geographical origin, VZV is genetically stable, and unrelated isolates exhibit little variability in virulence Tegument and capsid proteins in skin infection Like other herpesviruses, the VZV genome has duplicate copies of genes in the repeat regions, including those that encode the tegument proteins, IE62 encoded by orf62 and orf71 , IE63 encoded by orf63 and orf70 and ORF64 protein encoded by orf64 and orf69 1 , 7 BOX 1.

Neurotropism Before the DRG-xenograft model was developed, VZV neurotropism in human tissues could only be examined in sensory ganglia that were obtained at autopsy. Figure 4. VZV neurotropism in DRG xenografts 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 cells 27 left panel.

Perspective These studies in the SCID mouse model show that virus—host cell interactions result in a well-regulated infectious process in each of the tissue microenvironments that is important for VZV pathogenesis.

Acknowledgments The authors thank M. Footnotes Competing interests statement The authors declare no competing interests. References 1. Arvin AM, Gilden D. In: Fields Virology. Knipe D, Howley P, editors. Ku CC, et al. This paper shows the role of T cells in the transport of VZV and the control of replication by the potent innate response of skin cells. Gilden DH, et al. Varicella-zoster virus DNA in human sensory ganglia. Takahashi M. Clinical overview of varicella vaccine: development and early studies.

Perspectives on vaccines against varicella-zoster virus infections. Curr Top Microbiol Immunol. Weibel RE, et al. Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med. Cohen JI. The varicella-zoster virus genome. Chen JJ, et al. Mannose 6-phosphate receptor dependence of varicella zoster virus infection in vitro and in the epidermis during varicella and zoster.

Suenaga T, et al. Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses. Varicella-zoster virus IE62 protein utilizes the human mediator complex in promoter activation. J Virol. This paper documents the VZV takeover of the host cell gene transcription complex for viral gene transcription in combination with the IE62 major viral transactivator.

Ruyechan WT. Roles of cellular transcription factors in VZV replication. Moffat JF, et al. Besser J, et al. Differentiation of varicella-zoster virus ORF47 protein kinase and IE62 protein binding domains and their contributions to replication in human skin xenografts in the SCID-hu mouse.

Erazo A, Kinchington PR. Varicella-zoster virus open reading frame 66 protein kinase and its relationship to alphaherpesvirus US3 kinases. Schaap A, et al.

T-cell tropism and the role of ORF66 protein in pathogenesis of varicella-zoster virus infection. Schaap-Nutt A, et al. ORF66 protein kinase function is required for T-cell tropism of varicella-zoster virus in vivo. Eisfeld AJ, et al. This paper shows the role of the ORF66 viral kinase in activating the transcriptional function of IE The replication cycle of varicella-zoster virus: analysis of the kinetics of viral protein expression, genome synthesis, and virion assembly at the single-cell level.

This study documents the dynamics of VZV protein expression, genome replication and progeny virus assembly in newly infected cells from entry to virion release. Overview of varicella-zoster virus glycoproteins gC, gH and gL. Maresova L, et al. Characterization of interaction of gH and gL glycoproteins of varicella-zoster virus: their processing and trafficking. J Gen Virol. Vleck SE, et al. Anti-glycoprotein H antibody impairs the pathogenicity of varicella-zoster virus in skin xenografts in the SCID mouse model.

Structure—function analysis of varicella-zoster virus glycoprotein H identifies domain-specific roles for fusion and skin tropism. This study maps the functional domains in the gH ectodomain that are required for replication and skin infection.

Oliver SL, et al. Mutagenesis of varicella-zoster virus glycoprotein B: putative fusion loop residues are essential for viral replication, and the furin cleavage motif contributes to pathogenesis in skin tissue in vivo.

An immunoreceptor tyrosine-based inhibition motif in varicella-zoster virus glycoprotein B regulates cell fusion and skin pathogenesis. This paper shows that the gB cytoplasmic domain has a previously unrecognized motif that mimicks cellular ITIMs and that must be phosphorylated to control the fusogenic properties of gB and the detrimental effects of exaggerated cell fusion on VZV infection of skin.

Attenuation of the vaccine Oka strain of varicella-zoster virus and role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse. Zerboni L, et al. Varicella-zoster virus infection of human dorsal root ganglia in vivo. Abendroth A, et al. Varicella-zoster virus infection of human dendritic cells and transmission to T cells: implications for virus dissemination in the host. This paper shows the capacity of VZV to infect dendritic cells in skin and their capacity to transfer the virus into T cells.

Huch JH, et al. Impact of varicella-zoster virus on dendritic cell subsets in human skin during natural infection. Sen N, et al. STAT3 activation and survivin induction by varicella zoster virus promotes viral replication and skin pathogenesis. This paper shows that VZV, which is a lytic herpesvirus, induces STAT3 activation — leading to survivin expression, which was previously associated with oncogenic herpesviruses — and that takeover of this cellular pathway is necessary for VZV skin infection.

Functions of C-terminal domain of varicella-zoster virus glycoprotein E in viral replication in vitro and skin and T-cell tropism in vivo. Differential requirement for cell fusion and virion formation in the pathogenesis of varicella-zoster virus infection of skin and T cells. Koropchak CM, et al. Investigation of varicella-zoster virus infection of lymphocytes by in situ hybridization.

Ozaki T, et al. Viremic phase in nonimmunocompromised children with varicella. J Pediatr. Arvin AM, et al. Varicella-zoster virus T cell tropism and the pathogenesis of skin infection. Berarducci B, et al. Deletion of the first cysteine-rich region of the varicella-zoster virus glycoprotein E ectodomain abolishes the gE and gI interaction and differentially affects cell—cell spread and viral entry.

Functions of the unique N-terminal region of glycoprotein E in the pathogenesis of varicella-zoster virus infection. This study identifies a large non-conserved region of gE and maps its functions in skin infection.

Li Q, et al. Insulin degrading enzyme induces a conformational change in varicella-zoster virus gE, and enhances virus infectivity and stability. Glycoprotein I of varicella-zoster virus is required for viral replication in skin and T cells.

Ito H, et al. This paper reports that cell transcription factors have an essential role as determinants of VZV pathogenesis. Varicella-zoster virus open reading frame 10 is a virulence determinant in skin cells but not in T cells in vivo.

Baiker A, et al. The immediate-early 63 protein of varicella-zoster virus: analysis of functional domains required for replication in vitro and T cell and skin tropism in the SCIDhu model in vivo.

Kinchington PR, et al. Virion association of IE62, the varicella-zoster virus VZV major transcriptional regulatory protein, requires expression of the VZV open reading frame 66 protein kinase. Downregulation of class I major histocompatibility complex surface expression by varicella-zoster virus involves open reading frame 66 protein kinase-dependent and -independent mechanisms.

Varicella zoster virus immune evasion strategies. Bontems S, et al. Phosphorylation of varicella-zoster virus IE63 protein by casein kinase influences its cellular localization and gene regulation activity. J Biol Chem. Sommer MH, et al. Hoover SE, et al. Zuranski T, et al. Niizuma T, et al. Construction of varicella-zoster virus recombinants from parent Oka cosmids and demonstration that ORF65 protein is dispensable for infection of human skin and T cells in the SCID-hu mouse model.

Peng H, et al. Interaction between the varicella-zoster virus IE62 major transactivator and cellular transcription factor SP1. Cellular and viral factors regulate the varicella-zoster virus gE promoter during viral replication. The early immune response in healthy and immunocompromised subjects with primary varicella-zoster virus infection.

J Infect Dis. Schmid DS. Varicella-zoster virus vaccine: molecular genetics. VZV infection of keratinocytes: production of cell-free infectious virions in vivo. This paper reviews the process of VZV replication and release of cell-free virus into cutaneous skin lesions that are needed for transmission to other susceptible individuals.

Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3 IRF3 phosphorylation at key serine residues: a novel mechanism of IRF3 inhibition among herpesviruses. Vandevenne P, et al. The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.

Varicella-Zoster virus IE63, a major viral latency protein, is required to inhibit the alpha interferon-induced antiviral response.

Autophagosome formation during varicella-zoster virus infection following endoplasmic reticulum stress and the unfolded protein response. This paper shows the role of autophagy in the intrinsic response of skin cells to VZV infection. Reichelt M, et al. Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

PLoS Pathog. Chickenpox first occurs as a blister-like skin rash and fever. It takes from days after exposure for someone to develop chickenpox. The sores commonly occur in batches with different stages bumps, blisters, and sores present at the same time. The blisters usually scab over in 5 days. A person with chickenpox is contagious days before the rash appears and until all blisters have formed scabs. Children with weakened immune systems may have blisters occurring for a prolonged time period.

Adults can develop severe pneumonia and other serious complications. Shingles occurs when the virus, which has been inactive for some time, becomes active again. Severe pain and numbness along nerve pathways, commonly on the trunk or on the face, are present. Clusters of blisters appear 1 to 5 days later. The blisters are usually on one side of the body and closer together than in chickenpox.

Shingles does not spread as shingles from one person to another. If people who have never had chickenpox come in contact with the fluid from shingles blisters, they can develop chickenpox.

Vaccinated persons who get chickenpox generally have fewer than 50 spots or bumps, which may resemble bug bites more than typical, fluid-filled chickenpox blisters.