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The vaccinia virus A35R protein inhibits antigen presentation and suppresses cytokine synthesis by responding CD4+ T cells
Author(s) -
Rehm Kristina Elizabeth,
Connor Ramsey,
Jones Gwendolyn,
Mannie Mark,
Roper Rachel L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.855.15
Subject(s) - antigen presentation , antigen processing , biology , antigen , major histocompatibility complex , immune system , virology , vaccinia , t cell , antigen presenting cell , immunology , gene , genetics , recombinant dna
An adaptive immune response is initiated when an antigen presenting cell (APC) presents foreign antigen via major histocompatibility complex class II (MHC II) molecules to antigen‐specific CD4+ T cells. Many viruses, such as poxviruses, have evolved strategies to evade the host adaptive immune response. The poxvirus A35R protein is conserved in all 98 sequenced mammalian tropic poxviruses and has little homology to any non‐pox protein, suggesting an important and novel function. The A35R protein was not required for viral replication in any cell tested thus far, but was required for full virulence in the mouse model. It was therefore hypothesized that the A35R protein regulated aspects of the host immune response. In a model antigen presentation system, the presence of A35R caused a decrease in the amount of numerous cytokines that are produced during antigen presentation. Further data indicated that it is the APCs, and not the T‐cells, that are directly affected by A35R. Furthermore, A35R appears to localize to an endosomal compartment within the APC, where it can regulate many aspects of the MHC II antigen processing and presentation pathway. Because A35R is immunosuppressive, its removal from live virus vaccines should create more immunogenic vaccine strains.