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

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 (Fisher'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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Zhu B,Xiao Y,Yeager M,Clifford G,Wentzensen N,Cullen M,Boland JF,Bass S,Steinberg MK,Raine-Bennett T,Lee D,Burk RD,Pinheiro M,Song L,Dean M,Nelson CW,Burdett L,Yu K,Roberson D,Lorey T,Franceschi S,Castle PE,Wa

doi

10.1038/s41467-020-14730-1

subject

Has Abstract

pub_date

2020-02-14 00:00:00

pages

886

issue

1

issn

2041-1723

pii

10.1038/s41467-020-14730-1

journal_volume

11

pub_type

杂志文章

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