Inhibition of protein trafficking by coxsackievirus b3: multiple viral proteins target a single organelle.
Despite replicating to very high titers, coxsackieviruses do not elicit strong CD8 T-cell responses, perhaps because antigen presentation is inhibited by virus-induced disruption of host protein trafficking. Herein, we evaluated the effects of three viral nonstructural proteins (2B, 2BC, and 3A) on intracellular trafficking. All three of these proteins inhibited secretion, to various degrees, and directly associated with the Golgi complex, causing trafficking proteins to accumulate in this compartment. The 3A protein almost completely ablated trafficking and secretion, by moving rapidly to the Golgi, and causing its disruption. Using an alanine-scanning 3A mutant, we show that Golgi targeting and disruption can be uncoupled. Thus, coxsackieviruses rely on the combined effects of several gene products that target a single cellular organelle to successfully block protein secretion during an infection. These findings have implications for viral pathogenesis.
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
D019943:Amino Acid Substitution; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004769:Enterovirus Infections / Q000276:immunology* / Q000378:metabolism; D006056:Golgi Apparatus / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D017354:Point Mutation; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C500427:3A protein, coxsackievirus B; D014764:Viral Proteins