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Heat Increases the Editing Efficiency of Human Papillomavirus E2 Gene by Inducing Upregulation of APOBEC3A and 3G.

Abstract
Apolipoprotein B mRNA-editing catalytic polypeptide (APOBEC) 3 proteins have been identified as potent viral DNA mutators and have broad antiviral activity. In this study, we demonstrated that apolipoprotein B mRNA-editing catalytic polypeptide 3A (A3A) and A3G expression levels were significantly upregulated in human papillomavirus (HPV)-infected cell lines and tissues. Heat treatment resulted in elevated expression of A3A and A3G in a temperature-dependent manner in HPV-infected cells. Correspondingly, HPV-infected cells heat-treated at 44 °C showed accumulated G-to-A or C-to-T mutation in HPV E2 gene. Knockdown of A3A or A3G could promote cell viability, along with the lower frequency of A/T in HPV E2 gene. In addition, regressing genital viral warts also harbored high G-to-A or C-to-T mutation in HPV E2 gene. Taken together, we demonstrate that apolipoprotein B mRNA-editing catalytic polypeptide 3 expression and editing function was heat sensitive to a certain degree, partly explaining the mechanism of action of local hyperthermia to treat viral warts.
AuthorsYang Yang, Hexiao Wang, Xinrui Zhang, Wei Huo, Ruiqun Qi, Yali Gao, Gaofeng Zhang, Bing Song, Hongduo Chen, Xinghua Gao
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 137 Issue 4 Pg. 810-818 (04 2017) ISSN: 1523-1747 [Electronic] United States
PMID27890786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Proteins
  • RNA, Messenger
  • APOBEC3A protein, human
  • Cytidine Deaminase
Topics
  • Cells, Cultured
  • Condylomata Acuminata (genetics, therapy, virology)
  • Cytidine Deaminase (genetics)
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation
  • Humans
  • Hypothermia, Induced (methods)
  • Male
  • Papillomaviridae (genetics)
  • Papillomavirus Infections (genetics, pathology, therapy)
  • Proteins (genetics)
  • RNA, Messenger (genetics)
  • Sensitivity and Specificity
  • Up-Regulation

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