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Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance

  1. Author:
    Zhu, Bin
    Xiao, Yanzi
    Yeager,Meredith
    Clifford, Gary [ORCID]
    Wentzensen, Nicolas
    Cullen,Michael
    Boland,Joseph [ORCID]
    Bass,Sara
    Steinberg,Mia
    Raine-Bennett, Tina
    Lee, DongHyuk
    Burk, Robert D
    Pinheiro, Maisa
    Song,Lei
    Dean, Michael [ORCID]
    Nelson, Chase W [ORCID]
    Burdett,Laurie
    Yu, Kai
    Roberson, David
    Lorey, Thomas
    Franceschi, Silvia
    Castle, Philip E
    Walker, Joan
    Zuna, Rosemary
    Schiffman, Mark
    Mirabello, Lisa

  2. Author Address

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon, Cedex 08, France., Women 39;s Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Departments of Pediatrics, Microbiology and Immunology, and Obstetrics & Gynecology and Women 39;s Health, Albert Einstein College of Medicine, Bronx, NY, USA., Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, USA., Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA, USA., CRO Aviano National Cancer Institute IRCCS, Aviano, Italy., University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. mirabellol@mail.nih.gov.,
    1. Year: 2020
    2. Date: Feb 14
    3. Epub Date: 2020 02 14
  2. Journal: Nature communications
    1. 11
    2. 1
    3. Pages: pii: 10.1038/s41467-020-14730-1
  4. Type of Article: Article
  5. Article Number: 886
  6. ISSN: 2041-1723
  1. Abstract:

    HPV16 causes half of cervical cancers worldwide; for unknown reasons, most infections resolve within two years. Here, we analyze the viral genomes of 5,328 HPV16-positive case-control samples to investigate mutational signatures and the role of human APOBEC3-induced mutations in viral clearance and cervical carcinogenesis. We identify four de novo mutational signatures, one of which matches the COSMIC APOBEC-associated signature 2. The viral genomes of the precancer/cancer cases are less likely to contain within-host somatic HPV16 APOBEC3-induced mutations 160;(Fisher 39;s exact test, P = 6.2 x 10-14), and have a 30% lower nonsynonymous APOBEC3 mutation burden compared to controls. We replicate the low prevalence of HPV16 APOBEC3-induced mutations in 1,749 additional cases. APOBEC3 mutations also historically contribute to the evolution of HPV16 lineages. We demonstrate that cervical infections with a greater burden of somatic HPV16 APOBEC3-induced mutations are more likely to be benign or subsequently clear, suggesting they may reduce persistence, and thus progression, within the host.

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  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1038/s41467-020-14730-1
  3. PMID: 32060290
  4. View record in Web of Science®
  5. WOS: 000564260600003
  6. PII : 10.1038/s41467-020-14730-1

Library Notes

  1. Fiscal Year: FY2019-2020
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