Vaccinia virus A35R inhibits MHC class II antigen presentation

Abstract The Vaccinia virus gene A35R (Copenhagen designation) is highly conserved in mammalian-tropic poxviruses and is an important virulence factor, but its function was unknown. We show herein that A35 does not affect viral infectivity, apoptosis induction, or replication; however, we found that...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2010-02, Vol.397 (1), p.176-186
Main Authors: Rehm, Kristina E, Connor, Ramsey F, Jones, Gwendolyn J.B, Yimbu, Kenneth, Roper, Rachel L
Format: Article
Language:English
Subjects:
Animals
Antigen presentation
Antigen Presentation - immunology
Apoptosis
Chemokines
Cytokine
Cytokines
endosomes
Endosomes - chemistry
Histocompatibility Antigens Class II - immunology
Infectious Disease
Infectivity
Lymphocytes T
Macrophage
Major histocompatibility complex
MHC
Poxvirus
Rats
Replication
T-Lymphocytes - immunology
Vaccinia
Vaccinia virus
Vaccinia virus - immunology
Viral Proteins - analysis
Viral Proteins - immunology
virulence factors
Virulence Factors - analysis
Virulence Factors - immunology
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Summary:Abstract The Vaccinia virus gene A35R (Copenhagen designation) is highly conserved in mammalian-tropic poxviruses and is an important virulence factor, but its function was unknown. We show herein that A35 does not affect viral infectivity, apoptosis induction, or replication; however, we found that A35 significantly inhibited MHC class II-restricted antigen presentation, immune priming of T lymphocytes, and subsequent chemokine and cytokine synthesis. A35 localized to endosomes and reduced the amount of a model antigenic peptide displayed in the cleft of class II MHC. In addition, A35 decreased VV specific T cell responses in vivo. Thus, this is the first report identifying a function for the A35 protein in virulence as well as the first report identifying a VV gene that inhibits peptide antigen presentation.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2009.11.008