Persistent Human Papillomavirus Infection

Abstract

Simple Summary The success of HPV as an infectious agent lies not within its ability to cause disease, but rather in the adeptness of the virus to establish long-term persistent infection. The ability of HPV to replicate and maintain its genome in a stratified epithelium is contingent on the manipulation of many host pathways. HPVs must abrogate host anti-viral defense programs, perturb the balance of cellular proliferation and differentiation, and hijack DNA damage signaling and repair pathways to replicate viral DNA in a stratified epithelium. Together, these characteristics contribute to the ability of HPV to achieve long-term and persistent infection and to its evolutionary success as an infectious agent. Abstract Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.