Evidence for Editing of Human Papillomavirus DNA by APOBEC3 in Benign and Precancerous Lesions

• Published in: Science (American Association for the Advancement of Science) Vol. 320; no. 5873; pp. 230 - 233
• Main Authors: Vartanian, Jean-Pierre, Guétard, Denise, Henry, Michel, Wain-Hobson, Simon
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 11.04.2008; The American Association for the Advancement of Science; American Association for the Advancement of Science (AAAS)
• Subjects: AIDS; APOBEC Deaminases; Biological and medical sciences; Biopsies; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cervix Uteri; Cervix Uteri - virology; Cytidine; Cytidine - metabolism; Cytidine Deaminase; Cytosine Deaminase; Cytosine Deaminase - metabolism; Deoxyribonucleic acid; DNA; DNA Mismatch Repair; DNA, Viral; DNA, Viral - genetics; DNA, Viral - metabolism; Enzymes; Female; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genome, Viral; Genomes; Human papillomavirus; Human papillomavirus 16; Human papillomavirus 16 - genetics; Humans; Keratinocytes; Molecular and cellular biology; Molecular biology; Mupapillomavirus; Mupapillomavirus - genetics; Mutation; Papillomavirus Infections; Papillomavirus Infections - enzymology; Papillomavirus Infections - virology; Plasmids; Precancerous Conditions; Precancerous Conditions - enzymology; Precancerous Conditions - virology; Replication origin; Sequencing; Transfection; Uterine Cervical Neoplasms; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - virology; Virology; Warts; Warts - enzymology; Warts - virology; Human; Premalignant lesion; Enzyme; Papovaviridae; Malignant tumor; Papillomavirus; Virus; Human papillomavirus; DNA; Hydrolases; Mutation; Cancer; Cytidine deaminase
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1153201

Cytidine deaminases of the APOBEC3 family all have specificity for single-stranded DNA, which may become exposed during replication or transcription of double-stranded DNA. Three human APOBEC3A (hA3A), hA3B, and hA3H genes are expressed in keratinocytes and skin, leading us to determine whether genetic editing of human papillomavirus (HPV) DNA occurred. In a study of HPV1a plantar warts and HPV16 precancerous cervical biopsies, hyperedited HPV1a and HPV16 genomes were found. Strictly analogous results were obtained from transfection experiments with HPV plasmid DNA and the three nuclear localized enzymes: hA3A, hA3C, and hA3H. Thus, stochastic or transient overexpression of APOBEC3 genes may expose the genome to a broad spectrum of mutations that could influence the development of tumors.