Human papillomavirus (HPV)

Although a class I virus like HSV, HPV shows several major differences in its replication cycle. The dsDNA genome is circular and replicates within the cell nucleus, but the virus does not encode a DNA polymerase and hence relies much more on cellular enzymes than HSV. Early gene transcription produces several proteins. Two early pro- teins, E1 and E2, redirect cellular RNA polymerase and DNA polymerase to the expression and replication of the viral genome, while the early proteins E6 and E7 ensure that DNA polymerase is continuously available within infected cells. These proteins bind with and inhibit two cellular tumor suppressor proteins, retinoblastoma and p53, which regulate mitosis. Binding of E6 and E7 with retinoblastoma and p53 forces infected cells to enter the mitotic cycle, synthesizing DNA polymerase; virus proteins E1 and E2 direct the enzyme to replication of the virus genome as well as the cellular chromosomes. Unlike HSV, the predominant mechanism of replication is thought to be bidirectional, producing circular genomic DNA molecules but recent evidence has suggested that a rolling circle mechanism may also occur in differentiating cells of the upper epithelium. Because HPV infection causes mitosis the replicating virus genomes divide between the daughter cells, a feature that contributes to the persistence of the virus in the epithelium.

HPV encodes two late proteins (the capsid proteins L1 and L2) that are not synthesized until the infected cells move from the basal to the outer layer of the stratified epithelium and have matured. It is presumed that the promoter regulating expression of the late genes requires transcription factors not present in the basal (dividing) cells of the epithelium.