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

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

Nature communications, 2020-02, Vol.11 (1), p.886-12, Article 886 [Periódico revisado por pares]

England: Nature Publishing Group UK

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Título:
Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance
Autor: Zhu, Bin ; Xiao, Yanzi ; Yeager, Meredith ; Clifford, Gary ; Wentzensen, Nicolas ; Cullen, Michael ; Boland, Joseph F ; Bass, Sara ; Steinberg, Mia K ; Raine-Bennett, Tina ; Lee, DongHyuk ; Burk, Robert D ; Pinheiro, Maisa ; Song, Lei ; Dean, Michael ; Nelson, Chase W ; Burdett, Laurie ; Yu, Kai ; Roberson, David ; Lorey, Thomas ; Franceschi, Silvia ; Castle, Philip E ; Walker, Joan ; Zuna, Rosemary ; Schiffman, Mark ; Mirabello, Lisa
Assuntos: Adult ; APOBEC Deaminases ; Case-Control Studies ; Cervix Uteri - virology ; Cytidine Deaminase - genetics ; Cytidine Deaminase - metabolism ; Female ; Genome, Viral ; Host-Pathogen Interactions ; Human papillomavirus 16 - genetics ; Human papillomavirus 16 - physiology ; Humans ; Middle Aged ; Mutation ; Papillomavirus Infections - enzymology ; Papillomavirus Infections - genetics ; Papillomavirus Infections - virology ; Uterine Cervical Neoplasms - enzymology ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - virology
É parte de: Nature communications, 2020-02, Vol.11 (1), p.886-12, Article 886
Descrição: 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 ), 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.
Editor: England: Nature Publishing Group UK
Idioma: Inglês

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

England: Nature Publishing Group UK

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