Vaccinia virus A35R inhibits MHC class II antigen presentation.
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.
Rehm
Kristina E
KE
Brody School of Medicine at East Carolina University, Department of Microbiology and Immunology, Greenville, NC, USA.
Connor
Ramsey F
RF
Jones
Gwendolyn J B
GJ
Yimbu
Kenneth
K
Roper
Rachel L
RL
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D011992:Endosomes / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000032:analysis / Q000276:immunology*; D037521:Virulence Factors / Q000032:analysis / Q000276:immunology*
C547103:A35R protein, Vaccinia virus; D000949:Histocompatibility Antigens Class II; D014764:Viral Proteins; D037521:Virulence Factors