The Role of DCT in HPV16 Infection of HaCaTs

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 requ...

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Bibliographic Details
Published in:PloS one 2017-01, Vol.12 (1), p.e0170158-e0170158
Main Authors: Aksoy, Pınar, Meneses, Patricio I
Format: Article
Language:English
Subjects:
Amyloid Precursor Protein Secretases - metabolism
Biology and life sciences
Biosynthesis
Cell cycle
Cells, Cultured
Deoxyribonucleic acid
Dihydroxyphenylalanine
DNA
DNA damage
DNA, Viral - genetics
Dopachrome isomerase
Endoplasmic reticulum
Endoplasmic Reticulum - enzymology
Endoplasmic Reticulum - virology
Genetic screening
Genomes
Genotypes
Health risks
Heparan sulfate
Human papillomavirus
Human papillomavirus 16 - enzymology
Humans
Infections
Intramolecular Oxidoreductases - antagonists & inhibitors
Intramolecular Oxidoreductases - genetics
Intramolecular Oxidoreductases - metabolism
Keratinocytes - enzymology
Keratinocytes - pathology
Keratinocytes - virology
Localization
Medicine and Health Sciences
Melanoma
Nuclei
Nuclei (cytology)
Oxidative stress
Oxygen
Papillomaviridae
Papillomavirus infections
Papillomavirus Infections - genetics
Papillomavirus Infections - metabolism
Papillomavirus Infections - virology
Proteins
Reactive oxygen species
Reactive Oxygen Species - metabolism
RNA, Small Interfering - genetics
siRNA
Virology
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0170158