Human papillomavirus DNA replication - Interactions between the viral E1 protein and two subunits of human DNA polymerase alpha/primase

Papovaviruses are valuable models for the study of DNA replication in highe r eukaryotic organisms, as they depend on host factors for replication of t heir DNA. In this study we investigate the interactions between the human p apillomavirus type 11 (HPV-11) origin recognition and initiator protein E1 and human polymerase alpha/primase (pol alpha/primase) subunits, By using a variety of physical assays, we show that both 180- (p180) and 70-kDa (p70) subunits of pol alpha/primase interact with HPV-11 E1, The interactions of E1 with p180 and p70 are functionally different in cell-free replication o f an HPV-11 origin-containing plasmid, Exogenously added p180 inhibits both E2-dependent and E2-independent cell-free replication of HPV-11, whereas p 70 inhibits E2-dependent but stimulates ES-independent replication. Our exp eriments indicate that p70 does not physically interact with E2 and suggest that it may compete with E2 for binding to E1, A model of how E2 and p70 s equentially interact with E1 during initiation of viral DNA replication is proposed.