title: Human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes.
abstract: Human papillomavirus (HPV) infection is severely limited in its natural host, primary human keratinocytes. Our data show HPV infectivity in primary keratinocytes is over 100- and 1,000-fold lower than in established keratinocyte cell lines NIKS and HaCaT, respectively. Here, we show that the basal level of autophagy in primary human foreskin keratinocytes (HFKs) is higher than in immortalized keratinocytes, and that HPV16 virions significantly induce autophagy in HFKs. Interestingly, HPV16 infectivity is dramatically enhanced by knockdown of essential autophagy genes as well as biochemical inhibition of autophagy. The increase in HPV16 infectivity by autophagy inhibition is most significant in HFKs, showing an inverse correlation with basal HPV16 infectivity in HFK, NIKS, HaCaT, and 293FT cells. Further, inhibition of autophagy delays degradation of HPV16 capsid proteins during virus trafficking, indicating that host autophagy induced by HPV16 virions inhibits infection of primary keratinocytes through rapid degradation of viral capsid proteins.
authors.affiliation: Department of Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, United States.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Griffin
authors.forename: Louis
authors.initials: L
authors.lastname: Cicchini
authors.forename: Dohun
authors.initials: D
authors.lastname: Pyeon
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D057809:HEK293 Cells; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology* / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D034741:RNA, Small Interfering; C025946:3-methyladenine; D019869:Phosphatidylinositol 3-Kinases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D000225:Adenine