Coxsackievirus B3 proteins directionally complement each other to downregulate surface major histocompatibility complex class I.
Picornaviruses carry a small number of proteins with diverse functions that subvert and exploit the host cell. We have previously shown that three coxsackievirus B3 (CVB3) proteins (2B, 2BC, and 3A) target the Golgi complex and inhibit protein transit. Here we investigate these effects in more detail and evaluate the distribution of major histocompatibility complex (MHC) class I molecules, which are critical mediators of the CD8(+) T-cell response. We report that concomitant with viral protein synthesis, MHC class I surface expression is rapidly downregulated during infection. However, this phenomenon may not result solely from inhibition of anterograde trafficking; we propose a new mechanism whereby the CVB3 2B and 2BC proteins upregulate the internalization of MHC class I (and possibly other surface proteins), perhaps by focusing of endocytic vesicles at the Golgi complex. Thus, our findings indicate that CVB3 carries at least three nonstructural proteins that directionally complement one another; 3A disrupts the Golgi complex to inhibit anterograde transport, while 2B and/or 2BC upregulates endocytosis, rapidly removing proteins from the cell surface. Taken together, these effects may render CVB3-infected cells invisible to CD8(+) T cells and untouchable by many antiviral effector molecules. This has important implications for immune evasion by CVB3.
Cornell
Christopher T
CT
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Kiosses
William B
WB
Harkins
Stephanie
S
Whitton
J Lindsay
JL
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004769:Enterovirus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D014176:Protein Biosynthesis / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D022161:Transport Vesicles / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; C097017:coxsackie B3 virus protein 2B