Identification of the Orthopoxvirus
            <i>p4c</i>
            Gene, Which Encodes a Structural Protein That Directs Intracellular Mature Virus Particles into A-Type Inclusions

McKelvey, Terry A.; Andrews, Stanley C.; Miller, Sara; Ray, Caroline A.; Pickup, David J.

doi:10.1128/jvi.76.22.11216-11225.2002

Cited by 46 publications

(74 citation statements)

References 79 publications

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“…A25 is a truncated form of the cowpox virus (CPXV) A-type inclusion (ATI) matrix protein. Previous work has shown that A25 is required for the formation of the ATI and that A26 is needed for the attachment of virions to the ATI (103). The association of A26 with A25 supports a direct role of A26 in the embedding of virions within the ATI.…”

Section: Virus-virus Protein Interactionsmentioning

confidence: 57%

Poxvirus Proteomics and Virus-Host Protein Interactions

Vliet

Mohamed

Zhang

et al. 2009

Microbiol Mol Biol Rev

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SUMMARY Studies of the functional proteins encoded by the poxvirus genome provide information about the composition of the virus as well as individual virus-virus protein and virus-host protein interactions, which provides insight into viral pathogenesis and drug discovery. Widely used proteomic techniques to identify and characterize specific protein-protein interactions include yeast two-hybrid studies and coimmunoprecipitations. Recently, various mass spectrometry techniques have been employed to identify viral protein components of larger complexes. These methods, combined with structural studies, can provide new information about the putative functions of viral proteins as well as insights into virus-host interaction dynamics. For viral proteins of unknown function, identification of either viral or host binding partners provides clues about their putative function. In this review, we discuss poxvirus proteomics, including the use of proteomic methodologies to identify viral components and virus-host protein interactions. High-throughput global protein expression studies using protein chip technology as well as new methods for validating putative protein-protein interactions are also discussed.

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Section: Virus-virus Protein Interactionsmentioning

confidence: 57%

Poxvirus Proteomics and Virus-Host Protein Interactions

Vliet

Mohamed

Zhang

et al. 2009

Microbiol Mol Biol Rev

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“…The ATI matrix is formed by multiple copies of the A25L polypeptide, which corresponds to the CPXV158 protein (30). A26L, also named p4c or CPXV159 protein, is required to direct intracellular mature virions (IMVs) into ATIs (33); the protein has a bridging function between the A25L matrix protein and IMVs containing the membrane-associated A27L (CPXV162 protein) (34). In addition, the capability to embed mature virions in the ATIs was recently shown to influence the virulence of CPXV (35).…”

Section: Isolation Of a Cpxv From A Common Volementioning

confidence: 99%

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

Hoffmann

Franke

Jenckel

et al. 2015

J Virol

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The incidence of human cowpox virus (CPXV) infections has increased significantly in recent years. Serological surveys have suggested wild rodents as the main CPXV reservoir. We characterized a CPXV isolated during a large-scale screening from a feral common vole. A comparison of the full-length DNA sequence of this CPXV strain with a highly virulent pet rat CPXV isolate showed a sequence identity of 96%, including a large additional open reading frame (ORF) of about 6,000 nucleotides which is absent in the reference CPXV strain Brighton Red. Electron microscopy analysis demonstrated that the vole isolate, in contrast to the rat strain, forms A-type inclusion (ATI) bodies with incorporated virions, consistent with the presence of complete ati and p4c genes. Experimental infections showed that the vole CPXV strain caused only mild clinical symptoms in its natural host, while all rats developed severe respiratory symptoms followed by a systemic rash. In contrast, common voles infected with a high dose of the rat CPXV showed severe signs of respiratory disease but no skin lesions, whereas infection with a low dose led to virus excretion with only mild clinical signs. We concluded that the common vole is susceptible to infection with different CPXV strains. The spectrum ranges from well-adapted viruses causing limited clinical symptoms to highly virulent strains causing severe respiratory symptoms. In addition, the low pathogenicity of the vole isolate in its eponymous host suggests a role of common voles as a major CPXV reservoir, and future research will focus on the correlation between viral genotype and phenotype/ pathotype in accidental and reservoir species. IMPORTANCEWe report on the first detection and isolation of CPXV from a putative reservoir host, which enables comparative analyses to understand the infection cycle of these zoonotic orthopox viruses and the relevant genes involved. In vitro studies, including whole-genome sequencing as well as in vivo experiments using the Wistar rat model and the vole reservoir host allowed us to establish links between genomic sequences and the in vivo properties (virulence) of the novel vole isolate in comparison to those of a recent zoonotic CPXV isolated from pet rats in 2009. Furthermore, the role of genes present only in a reservoir isolate can now be further analyzed. These studies therefore allow unique insights and conclusions about the role of the rodent reservoir in CPXV epidemiology and transmission and about the zoonotic threat that these viruses represent. C owpox virus (CPXV), a member of the genus Orthopoxvirus (OPV) in the Poxviridae family, is suspected to be widespread in Western Eurasian rodents, particularly vole species (1, 2). From the presumed reservoir hosts, spill-over infections to accidental hosts are regularly observed (3). The accidental hosts include domestic cats and also exotic animals in zoos, such as large felids and elephants, which regularly develop severe disease (3). As CPXV is a zoonotic virus, humans in direct contact wit...

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“…The mechanism by which A26p mediates occlusion had not been elucidated, although a role in retrograde transport of MVs was suggested (15). Recently, A26p was shown to be anchored to the MV membrane through disulfide bonding with the A27 protein (A27p) (4,9), which is in turn tethered to the MV membrane through interactions with the A17 transmembrane protein (A17p) (19,24).…”

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confidence: 99%

“…This A25 protein (A25p) contains the N-terminal half of ATIp, including the first four ATIp repeats and six amino acids of the fifth repeat. The embedding of MVs in inclusions requires a protein encoded by homologs of the A26L gene, which is mutated in some orthopoxvirus strains (15,23). Although VACV does not form inclusion bodies, the VACV A26L gene (VACVWR149) is intact, and the VACV A26 protein (A26p) can complement the defective A26p homolog in the Brighton red (BR) strain of CPXV (CPXV-BR) (15).…”

mentioning

confidence: 99%

“…The embedding of MVs in inclusions requires a protein encoded by homologs of the A26L gene, which is mutated in some orthopoxvirus strains (15,23). Although VACV does not form inclusion bodies, the VACV A26L gene (VACVWR149) is intact, and the VACV A26 protein (A26p) can complement the defective A26p homolog in the Brighton red (BR) strain of CPXV (CPXV-BR) (15). Whether VACV is missing other proteins needed for inclusion formation and occlusion was not known prior to the present study.…”

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Congregation of Orthopoxvirus Virions in Cytoplasmic A-Type Inclusions Is Mediated by Interactions of a Bridging Protein (A26p) with a Matrix Protein (ATIp) and a Virion Membrane-Associated Protein (A27p)

Howard

Weisberg

Moss

2010

J Virol

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Some orthopoxviruses, e.g., the cowpox, ectromelia, and raccoonpox viruses, form large, discrete cytoplasmic inclusions within which mature virions (MVs) are embedded by a process called occlusion. These inclusions, which may protect occluded MVs in the environment, are composed of aggregates of the A-type inclusion protein (ATIp), which is truncated in orthopoxviruses such as vaccinia virus (VACV) and variola virus that fail to form inclusions. In addition to an intact ATIp, occlusion requires the A26 protein (A26p). Although VACV contains a functional A26p, determined by complementation of a cowpox virus occlusion-defective mutant, its role in occlusion was unknown. We found that restoration of the full-length ATI gene was sufficient for VACV inclusion formation and the ensuing occlusion of MVs. A26p was present in inclusions even when virion assembly was inhibited, suggesting a direct interaction of A26p with ATIp. Analysis of a panel of ATIp mutants indicated that the C-terminal repeat region was required for inclusion formation and the N-terminal domain for interaction with A26p and occlusion. A26p is tethered to MVs via interaction with the A27 protein (A27p); A27p was not required for association of A26p with ATIp but was necessary for occlusion. In addition, the C-terminal domain of A26p, which mediates A26p-A27p interactions, was necessary but insufficient for occlusion. Taken together, the data suggest a model for occlusion in which A26p has a bridging role between ATIp and A27p, and A27p provides a link to the MV membrane.

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Identification of the Orthopoxvirus p4c Gene, Which Encodes a Structural Protein That Directs Intracellular Mature Virus Particles into A-Type Inclusions

Cited by 46 publications

References 79 publications

Poxvirus Proteomics and Virus-Host Protein Interactions

Poxvirus Proteomics and Virus-Host Protein Interactions

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

Congregation of Orthopoxvirus Virions in Cytoplasmic A-Type Inclusions Is Mediated by Interactions of a Bridging Protein (A26p) with a Matrix Protein (ATIp) and a Virion Membrane-Associated Protein (A27p)

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