PMID- 25080100 OWN - NLM STAT- MEDLINE DCOM- 20150402 LR - 20231213 IS - 1553-7374 (Electronic) IS - 1553-7366 (Print) IS - 1553-7366 (Linking) VI - 10 IP - 7 DP - 2014 Jul TI - Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection. PG - e1004281 LID - 10.1371/journal.ppat.1004281 [doi] LID - e1004281 AB - Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1) cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA)-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection. FAU - Kim, Eun-Young AU - Kim EY AD - Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Lorenzo-Redondo, Ramon AU - Lorenzo-Redondo R AD - Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Little, Susan J AU - Little SJ AD - Division of Infectious Diseases, University of California San Diego, San Diego, California, United States of America. FAU - Chung, Yoon-Seok AU - Chung YS AD - Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Phalora, Prabhjeet K AU - Phalora PK AD - Department of Infectious Diseases, King's College London, Guy's Hospital, London, United Kingdom. FAU - Maljkovic Berry, Irina AU - Maljkovic Berry I AD - Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Archer, John AU - Archer J AD - Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. FAU - Penugonda, Sudhir AU - Penugonda S AD - Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Fischer, Will AU - Fischer W AD - Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America. FAU - Richman, Douglas D AU - Richman DD AD - Division of Infectious Diseases, University of California San Diego, San Diego, California, United States of America; Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America. FAU - Bhattacharya, Tanmoy AU - Bhattacharya T AD - Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America; Santa Fe Institute, Santa Fe, New Mexico, United States of America. FAU - Malim, Michael H AU - Malim MH AD - Department of Infectious Diseases, King's College London, Guy's Hospital, London, United Kingdom. FAU - Wolinsky, Steven M AU - Wolinsky SM AD - Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. LA - eng GR - G1000196/MRC_/Medical Research Council/United Kingdom GR - G0401570/MRC_/Medical Research Council/United Kingdom GR - R01 AI070072/AI/NIAID NIH HHS/United States GR - U01 AI043638/AI/NIAID NIH HHS/United States GR - G1001081/MRC_/Medical Research Council/United Kingdom GR - U01 AI035039/AI/NIAID NIH HHS/United States GR - P01 AI074621/AI/NIAID NIH HHS/United States GR - R24 AI106039/AI/NIAID NIH HHS/United States GR - P01 AI090935/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20140731 PL - United States TA - PLoS Pathog JT - PLoS pathogens JID - 101238921 RN - 0 (DNA, Viral) RN - EC 3.5.4.- (APOBEC3H protein, human) RN - EC 3.5.4.- (Aminohydrolases) RN - EC 3.5.4.1 (APOBEC3F protein, human) RN - EC 3.5.4.1 (Cytosine Deaminase) RN - EC 3.5.4.5 (APOBEC Deaminases) RN - EC 3.5.4.5 (APOBEC-3G Deaminase) RN - EC 3.5.4.5 (APOBEC3 proteins, human) RN - EC 3.5.4.5 (APOBEC3D protein, human) RN - EC 3.5.4.5 (APOBEC3G protein, human) RN - EC 3.5.4.5 (Cytidine Deaminase) SB - IM MH - APOBEC Deaminases MH - APOBEC-3G Deaminase MH - Adaptation, Physiological/*genetics MH - Aminohydrolases/genetics MH - Base Sequence MH - *Biological Evolution MH - Cytidine Deaminase/genetics MH - Cytosine Deaminase/*genetics MH - DNA, Viral/genetics MH - Genetic Variation/*genetics MH - Genome, Viral MH - HIV Infections/genetics/immunology/*virology MH - HIV-1/*genetics MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Molecular Sequence Data MH - Mutation/*genetics MH - Phylogeny MH - Polymerase Chain Reaction MH - Sequence Homology, Nucleic Acid MH - Virus Replication/genetics PMC - PMC4117599 COIS- The authors have declared that no competing interests exist. EDAT- 2014/08/01 06:00 MHDA- 2015/04/04 06:00 PMCR- 2014/07/31 CRDT- 2014/08/01 06:00 PHST- 2014/01/08 00:00 [received] PHST- 2014/06/13 00:00 [accepted] PHST- 2014/08/01 06:00 [entrez] PHST- 2014/08/01 06:00 [pubmed] PHST- 2015/04/04 06:00 [medline] PHST- 2014/07/31 00:00 [pmc-release] AID - PPATHOGENS-D-14-00062 [pii] AID - 10.1371/journal.ppat.1004281 [doi] PST - epublish SO - PLoS Pathog. 2014 Jul 31;10(7):e1004281. doi: 10.1371/journal.ppat.1004281. eCollection 2014 Jul.