title: The Role of DCT in HPV16 Infection of HaCaTs.
abstract: Persistent infection with high-risk human papillomavirus (HPV) genotype is a major factor leading to many human cancers. Mechanisms of HPV entry into host cells and genome trafficking towards the nucleus are incompletely understood. Dopachrome tautomerase (DCT) was identified as a cellular gene required for HPV infection in HeLa cells on a siRNA screen study. Here, we confirm that DCT knockdown significantly decreases HPV infection in the human keratinocyte HaCaT cells as was observed in HeLas. We investigated the effects of DCT knockdown and found that DCT depletion caused increased reactive oxygen species (ROS) levels, DNA damage and altered cell cycle in HaCaT cells. We observed increased viral DNA localization at the endoplasmic reticulum but an overall decrease in infection in DCT knockdown cells. This observation suggests that viral DNA might be retained in the ER due to altered cell cycle, and viral particles are incapable of further movement towards the nucleus in DCT knockdown cells.
authors.affiliation: Department of Biological Sciences, Fordham University, Bronx, New York, United States of America.
authors.forename: Pınar
authors.initials: P
authors.lastname: Aksoy
authors.affiliation: Department of Biological Sciences, Fordham University, Bronx, New York, United States of America.
authors.forename: Patricio I
authors.initials: PI
authors.lastname: Meneses
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000821:virology; D052162:Human papillomavirus 16 / Q000201:enzymology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D034741:RNA, Small Interfering / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053829:Amyloid Precursor Protein Secretases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase