Varying efficiency of long-term replication of papillomaviruses in Saccharomyces cerevisiae

Human papillomaviruses (HPVs) replicate in mitotically active basal keratinocytes. Two virally encoded proteins, E1, a helicase, and E2, a transcription factor, are important players in replication and maintenance of HPV episomes. We previously showed that HPV16 could replicate stably in Saccharomyces cerevisiae [Angeletti, P.C., Kim, K., Fernandes, F.J., and Lambert, P.F. (2002)] and we identified cis-elements that mediate replication and maintenance [J. Virol. 76(7), 3350-3358.; Kim, K., Angeletti, P.C., Hassebroek, E.C., and Lambert, P.F. (2005)]. Here, we demonstrate that although multiple HPV genomes replicate stably in yeast, they do so with differing long-term efficiency; HPV6-Ura3 is replicated at the highest copy number, followed by HPV31-Ura3 and HPV16-Ura3 respectively, HPV11-Ura3 and HPV18-Ura3 were unable replicate without the presence of E2 expression and BPV-1-Ura3 was unable to replicate, with or without the presence of E2. These studies suggest genotype-specific differences in HPV replication and maintenance.