GBF1, a cellular guanine nucleotide exchange factor, is required for poliovirus RNA replication, and its interaction with viral protein 3A determines the sensitivity of virus infection to brefeldin A.
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 et al. (Thu,) conducted a other in Poliovirus infection. GBF1 mutation or knockdown vs. Wild type GBF1 or control siRNA was evaluated on Poliovirus RNA replication. GBF1, a cellular guanine nucleotide exchange factor, is required for poliovirus RNA replication, and its interaction with viral protein 3A determines the sensitivity of virus infection to brefeldin A.