Human APOBEC3G drives HIV-1 evolution and the development of drug resistance

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Human APOBEC3G (hA3G) is an innate virus restriction factor that induces deamination of specific cytidine residues in single-stranded human immunodeficiency virus type 1 (HIV-1) DNA. Whereas destructive hA3G editing leads to a profound loss of HIV-1 infectivity, more limited editing could be a source of adaptation and diversification. Here we show that the presence of hA3G in T-cells can drive the development of diversity in HIV-1 populations and that under selection pressure imposed by the nucleotide analog reverse transcriptase inhibitor 3TC ((-)2',3'-dideoxy-3'-thiacytidine), a single point mutation that confers 3TC resistance, methionine 184 to isoleucine (M1841), emerges rapidly and reaches fixation. ... continued below

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Bhattacharya, Tamoy; Kim, Eun - Young; Koning, Fransje; Malim, Michael & Wolinsky, Steven M January 1, 2008.

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Human APOBEC3G (hA3G) is an innate virus restriction factor that induces deamination of specific cytidine residues in single-stranded human immunodeficiency virus type 1 (HIV-1) DNA. Whereas destructive hA3G editing leads to a profound loss of HIV-1 infectivity, more limited editing could be a source of adaptation and diversification. Here we show that the presence of hA3G in T-cells can drive the development of diversity in HIV-1 populations and that under selection pressure imposed by the nucleotide analog reverse transcriptase inhibitor 3TC ((-)2',3'-dideoxy-3'-thiacytidine), a single point mutation that confers 3TC resistance, methionine 184 to isoleucine (M1841), emerges rapidly and reaches fixation. These results provide strong evidence that mutation by hA3G is an important source of genetic variation on which natural selection acts to shape the structure of the viral population and drive the tempo of HIV-1 evolution.

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  • Journal Name: Science

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  • Report No.: LA-UR-08-07876
  • Report No.: LA-UR-08-7876
  • Grant Number: AC52-06NA25396
  • Office of Scientific & Technical Information Report Number: 956637
  • Archival Resource Key: ark:/67531/metadc930961

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  • January 1, 2008

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  • Nov. 13, 2016, 7:26 p.m.

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  • Dec. 12, 2016, 6:39 p.m.

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Bhattacharya, Tamoy; Kim, Eun - Young; Koning, Fransje; Malim, Michael & Wolinsky, Steven M. Human APOBEC3G drives HIV-1 evolution and the development of drug resistance, article, January 1, 2008; [New Mexico]. (digital.library.unt.edu/ark:/67531/metadc930961/: accessed July 19, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.