Vaccinia Virus Proteome: Identification of Proteins in Vaccinia Virus Intracellular Mature Virion Particles

Chung, Che-Sheng; Chen, Chein‐Hung; Ho, Ming‐Yi; Huang, Cheng‐Yen; Liao, Chung-Lin; Chang, Wen

doi:10.1128/jvi.80.5.2127-2140.2006

Cited by 227 publications

(243 citation statements)

References 192 publications

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“…There was no obvious relationship, however, between immunodominance, as assessed by hierarchies of IFN-␥ responder cell numbers (Fig. 6) or the presence of multiple epitopes per ORF (Table II) and protein occurrence in virions (55). A3L, for example, was dominant in subject 2 and contains at least 3 epitopes.…”

Section: Discussionmentioning

confidence: 90%

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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Vaccination with replication-competent vaccinia protects against heterologous orthopoxvirus challenge. CD4 T cells have essential roles helping functionally important Ab and CD8 antiviral responses, and contribute to the durability of vaccinia-specific memory. Little is known about the specificity, diversity, or dominance hierarchy of orthopoxvirus-specific CD4 T cell responses. We interrogated vaccinia-reactive CD4 in vitro T cell lines with vaccinia protein fragments expressed from an unbiased genomic library, and also with a panel of membrane proteins. CD4 T cells from three primary vaccinees reacted with 44 separate antigenic regions in 35 vaccinia proteins, recognizing 8 to 20 proteins per person. The integrated responses to the Ags that we defined accounted for 49 to 81% of the CD4 reactivity to whole vaccinia Ag. Individual dominant Ags drove up to 30% of the total response. The gene F11L-encoded protein was immunodominant in two of three subjects and is fragmented in a replication-incompetent vaccine candidate. The presence of protein in virions was strongly associated with CD4 antigenicity. These findings are consistent with models in which exogenous Ag drives CD4 immunodominance, and provides tools to investigate the relationship between Ab and CD4 T cell specificity for complex pathogens.

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Section: Discussionmentioning

confidence: 90%

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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“…ϩ T cells could be explained by the near complete absence of virulence factors in the virion (30). It is likely that DC take up debris from apoptotic or necrotic VACV-infected cells that might contain VACV virulence factors that theoretically could be presented by DC via MHC class II molecules.…”

Section: Cd8mentioning

confidence: 99%

Vaccinia Virus-Specific CD4+ T Cell Responses Target a Set of Antigens Largely Distinct from Those Targeted by CD8+ T Cell Responses

Moutaftsi

Bui

Peters

et al. 2007

The Journal of Immunology

100

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Recent studies have defined vaccinia virus (VACV)-specific CD8؉ T cell epitopes in mice and humans. However, little is known about the epitope specificities of CD4 ؉ T cell responses. In this study, we identified 14 I-A b -restricted VACV-specific CD4 ؉ T cell epitopes by screening a large set of 2146 different 15-mer peptides in C57BL/6 mice. These epitopes account for ϳ20% of the total anti-VACV CD4 T he CD4ϩ T cells play a central role in the host defense against invading pathogens. Several recent studies showed a critical role of CD4 ϩ T cells for eliciting an efficient memory CD8 ϩ T cell response against acute viral infections. Memory CD8 ϩ T cells primed in the absence of CD4 ϩ T cell help are qualitatively impaired in their ability to mount a vigorous response to secondary encounter with Ag (1-4). CD4ϩ T cells also help B cells to produce neutralizing Abs and play a critical role in generating B cell memory (5, 6). Finally, CD4ϩ T cells can directly impede the spread of viruses through the secretion of antiviral cytokines such as IFN-␥ that block viral replication, and cytotoxic functions have also been attributed to CD4 ϩ T cells (7,8).A clear role of CD4 ϩ T cells is apparent in infection with vaccinia virus (VACV) 3 . Immunization with VACV induces cellular immune responses that persist for Ͼ35 years (5, 9 -11). T cell immunity is most important for VACV resistance in naive mice (12). In contrast, Ab responses play a major role in protection against lethal challenge with VACV in immunized mice (12) or monkeypox virus in primates (13).In a recent study, a single modified vaccinia virus Ankara (MVA) inoculation protected mice deficient of B and CD8 ϩ T cells against lethal VACV intranasal challenge, whereas CD4 and MHC class II-deficient mice were poorly protected (14). Despite their importance, little is known about the breadth of VACV-specific CD4 ϩ T cell responses and the nature of the Ags recognized. In contrast, recent studies have defined the Ags and epitopes recognized by CD8 ϩ T cell responses following VACV infection in mice and humans (15-21). The breadth of CD8 ϩ T cell VACV responses is large with a total of 103 Ags recognized thus far in total, most of which are early Ags. CD8 ϩ T cells equally recognize VACV structural proteins, regulatory proteins, and virulence factors.To understand the impact of CD4 ϩ T cell responses and the dynamic development of CD8 ϩ T cell responses, it is important to similarly define the breadth and nature of CD4 ϩ T cell responses.Several studies have shown that the number of CD4 ϩ T cells involved in responses are of lower magnitude when compared with CD8 ϩ T cell responses, both in general and also in the case of VACV infection (22)(23)(24)(25). It is currently unknown whether this lower magnitude is due to the recognition of fewer epitopes, but with each epitope being recognized by responses of similar magnitude. Alternatively, it is possible that the overall lower CD4 ϩ T cell response is reflective of a comparable number of epitopes, each associated with ...

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“…However, most of these studies were limited in their ability to perform a complete structural analysis of all the protein components of the virion, possibly due to the limited availability of advanced purification techniques and the limitations of the technologies available for protein identification at the time of those studies. Ten years later, several studies of the comprehensive structural analysis of the protein composition of the infectious MV of VACV were reported (30,134,179). In one study, by analyzing the proteins in the MV of VACV-WR using a combination of gel-free liquid chromatography and tandem MS (LC-MS/MS), Chung et al identified 75 viral proteins and determined their relative abundances (Table 1) (30).…”

Section: Proteomic Studies Of Poxvirus Virionsmentioning

confidence: 99%

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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Vaccinia Virus Proteome: Identification of Proteins in Vaccinia Virus Intracellular Mature Virion Particles

Cited by 227 publications

References 192 publications

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Vaccinia Virus-Specific CD4+ T Cell Responses Target a Set of Antigens Largely Distinct from Those Targeted by CD8+ T Cell Responses

Poxvirus Proteomics and Virus-Host Protein Interactions

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