question: Replication of many (+)RNA viruses depends on the cellular protein GBF1, but its role in the replication process is not clear. In uninfected cells GBF1 activates small GTPases of the Arf family and coordinates multiple steps of membrane metabolism, including functioning of the cellular secretory pathway. A non-structural protein 3A of poliovirus and related viruses has been shown to directly interact with GBF1, likely mediating its recruitment to the replication complexes. Surprisingly, viral mutants with severely reduced level of 3A-GBF1 interaction demonstrate minimal replication defects in cell culture. Here we systematically investigated the conserved elements of GBF1 to understand what determinants are important to support poliovirus replication. We demonstrate that multiple GBF1 mutants inactive in cellular metabolism could still be fully functional in the replication complexes. Our results show that Arf activating property, but not the primary structure of the Sec7 domain is indispensable for viral replication. They also suggest a redundant mechanism of recruitment of GBF1 to the replication sites, dependent not only on direct interaction of the protein with the viral protein 3A, but also on determinants located in the non-catalytic C-terminal domains of GBF1. Such double targeting mechanism explains the previous observations of remarkable tolerance of different levels of GBF1-3A interaction by the virus, and likely constitutes an important element of resilience of viral replication.Importance. Enteroviruses are a vast group of viruses associated with diverse human diseases but only two of them could be controlled with vaccines, and effective anti-viral therapeutics are lacking. Here we investigated in details the contribution of a cellular protein GBF1 in the replication of poliovirus, a representative enterovirus. GBF1 supports functioning of cellular membrane metabolism and is recruited to viral replication complexes upon infection. Our resuts demonstrate that the virus requires a limited subset of the normal GBF1 functions, and reveal the elements of GBF1 essential to support viral replication under different conditions. Since diverse viruses often rely on the same cellular proteins for replication, understanding the mechanisms by which these proteins support infection is essential for the development of broad spectrum anti-viral therapeutics.