A critical role of a cellular membrane traffic protein in poliovirus RNA replication.
Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA.
Belov
George A
GA
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Feng
Qian
Q
Nikovics
Krisztina
K
Jackson
Catherine L
CL
Ehrenfeld
Ellie
E
D020126:Brefeldin A / Q000494:pharmacology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D015388:Organelles / Q000187:drug effects / Q000821:virology*; D017955:Poliovirus / Q000502:physiology*; D021381:Protein Transport; D012367:RNA, Viral / Q000235:genetics*; D014758:Viral Core Proteins / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*
C109349:3A protein, Poliovirus; C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D012367:RNA, Viral; D014758:Viral Core Proteins; D020126:Brefeldin A