Editing HIV (section)

====Recombination====
{{Further|Genetic recombination}}
Two RNA genomes are encapsidated in each HIV-1 particle (see [[Structure and genome of HIV]]). Upon infection and replication catalyzed by reverse transcriptase, recombination between the two genomes can occur.<ref name="Hu">{{cite journal | vauthors = Hu WS, Temin HM | title = Retroviral recombination and reverse transcription | journal = Science | volume = 250 | issue = 4985 | pages = 1227–33 | year = 1990 | pmid = 1700865 | doi = 10.1126/science.1700865 | bibcode = 1990Sci...250.1227H }}</ref><ref name="Charpentier">{{cite journal | vauthors = Charpentier C, Nora T, Tenaillon O, Clavel F, Hance AJ | title = Extensive recombination among human immunodeficiency virus type 1 quasispecies makes an important contribution to viral diversity in individual patients | journal = Journal of Virology | volume = 80 | issue = 5 | pages = 2472–82 | year = 2006 | pmid = 16474154 | pmc = 1395372 | doi = 10.1128/JVI.80.5.2472-2482.2006 }}</ref> Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle the genetic information that is transmitted from parental to progeny genomes.<ref name="Charpentier" />

Viral recombination produces genetic variation that likely contributes to the [[evolution]] of resistance to [[Management of HIV/AIDS|anti-retroviral therapy]].<ref>{{cite journal | vauthors = Nora T, Charpentier C, Tenaillon O, Hoede C, Clavel F, Hance AJ | title = Contribution of recombination to the evolution of human immunodeficiency viruses expressing resistance to antiretroviral treatment | journal = Journal of Virology | volume = 81 | issue = 14 | pages = 7620–8 | year = 2007 | pmid = 17494080 | pmc = 1933369 | doi = 10.1128/JVI.00083-07 }}</ref> Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It is unknown how often such mixed packaging occurs under natural conditions.<ref>{{cite journal | vauthors = Chen J, Powell D, Hu WS | title = High frequency of genetic recombination is a common feature of primate lentivirus replication | journal = Journal of Virology | volume = 80 | issue = 19 | pages = 9651–8 | year = 2006 | pmid = 16973569 | pmc = 1617242 | doi = 10.1128/JVI.00936-06 }}</ref>

Bonhoeffer ''et al.''<ref name=Bonhoeffer>{{cite journal | vauthors = Bonhoeffer S, Chappey C, Parkin NT, Whitcomb JM, Petropoulos CJ | title = Evidence for positive epistasis in HIV-1 | journal = Science | volume = 306 | issue = 5701 | pages = 1547–50 | year = 2004 | pmid = 15567861 | doi = 10.1126/science.1101786 | bibcode = 2004Sci...306.1547B | s2cid = 45784964 }}</ref> suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin<ref name=Hu /> suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of the adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process, the generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching.<ref name=Bonhoeffer />

HIV-1 infection causes [[chronic inflammation]] and production of [[reactive oxygen species]].<ref>{{cite journal | vauthors = Israël N, Gougerot-Pocidalo MA | title = Oxidative stress in human immunodeficiency virus infection | journal = Cellular and Molecular Life Sciences | volume = 53 | issue = 11–12 | pages = 864–70 | year = 1997 | pmid = 9447238 | doi = 10.1007/s000180050106 | s2cid = 22663454 | pmc = 11147326 }}</ref> Thus, the HIV genome may be vulnerable to [[oxidative damage]], including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod ''et al.''<ref name="pmid18295550">{{cite journal | vauthors = Michod RE, Bernstein H, Nedelcu AM | title = Adaptive value of sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 8 | issue = 3 | pages = 267–85 | date = May 2008 | pmid = 18295550 | doi = 10.1016/j.meegid.2008.01.002 | bibcode = 2008InfGE...8..267M | url = http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf | access-date = May 10, 2013 | archive-date = May 16, 2017 | archive-url = https://web.archive.org/web/20170516235741/http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf | url-status = dead }}</ref> suggested that recombination by viruses is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit.