title: Initial amplification of the HPV18 genome proceeds via two distinct replication mechanisms.
abstract: Determining the mechanism of HPV18 replication is paramount for identifying possible drug targets against HPV infection. We used two-dimensional and three-dimensional gel electrophoresis techniques to identify replication intermediates arising during the initial amplification of HPV18 episomal genomes. We determined that the first rounds of HPV18 replication proceed via bidirectional theta structures; however, a notable accumulation of almost fully replicated HPV18 genomes indicates difficulties with the completion of theta replication. We also observed intermediates that were created by a second replication mechanism during the initial amplification of HPV18 genomes. The second replication mechanism does not utilize specific initiation or termination sequences and proceeds via a unidirectional replication fork. We suggest a significant role for the second replication mechanism during the initial replication of the HPV18 genome and propose that the second replication mechanism is recombination-dependent replication.
authors.affiliation: University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
authors.forename: Marit
authors.initials: M
authors.lastname: Orav
authors.affiliation: University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
authors.forename: Jelizaveta
authors.initials: J
authors.lastname: Geimanen
authors.affiliation: University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Sepp
authors.affiliation: University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
authors.forename: Liisi
authors.initials: L
authors.lastname: Henno
authors.affiliation: University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.|Estonian Biocentre, Riia 23, 51010 Tartu, Estonia.
authors.forename: Ene
authors.initials: E
authors.lastname: Ustav
authors.affiliation: University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.|Icosagen Cell Factory OÜ, Eerika tee 1, 61713, Õssu, Estonia.|Estonian Academy of Sciences, Kohtu 6, 10130 Tallinn, Estonia.
authors.forename: Mart
authors.initials: M
authors.lastname: Ustav
mesh_terms: D002460:Cell Line; D004261:DNA Replication / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D010957:Plasmids / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*