Journal
FRONTIERS IN MICROBIOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2017.02250
Keywords
beta HPV; DNA-damage response; skin cancer; genomic fidelity; tumorigenesis; epidermodysplasia verruciformis; viral oncogenesis; p300
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Funding
- Department of Defense [CMDRP PRCRP CA160224]
- Les Clow family
- Johnson Cancer Research Center at Kansas State University
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While the role of genus alpha human papillomaviruses in the tumorigenesis and tumor maintenance of anogenital and oropharyngeal cancers is well-established, the role of genus beta human papilloviruses (beta-HPVs) in non-melanoma skin cancers (NMSCs) is less certain. Persistent beta-HPV infections cause NMSCs in sun-exposed skin of people with a rare genetic disorder, epidermodysplasia verruciformis. However, beta-HPV infections in people without epidermodysplasia verruciformis are typically transient. Further, beta-HPV gene expression is not necessary for tumor maintenance in the general population as on average there is fewer than one copy of the beta-HPV genome per cell in NMSC tumor biopsies. Cell culture, epidemiological, and mouse model experiments support a role for beta-HPV infections in the initiation of NMSCs through a hit and run mechanism. The virus is hypothesized to act as a cofactor, augmenting the genome destabilizing effects of UV. Supporting this idea, two beta-HPV proteins (beta-HPV E6 and E7) disrupt the cellular response to UV exposure and other genome destabilizing events by abrogating DNA repair and deregulating cell cycle progression. The aberrant damage response increases the likelihood of oncogenic mutations capable of driving tumorigenesis independent of a sustained beta-HPV infection or continued viral protein expression. This review summarizes what is currently known about the deleterious effects of beta-HPV on genome maintenance in the context of the virus's putative role in NMSC initiation.
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