hiv - everything you need to know 6
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7/27/2019 HIV - Everything You Need to Know 6
http://slidepdf.com/reader/full/hiv-everything-you-need-to-know-6 1/1
11/15/13 HIV - Wikipedia, the free encyclopedia
en.wikipedia.org/wiki/Human_immunodeficiency_virus 6/19
Reverse transcription of the HIV
genome into double strand DNA
During viral replication, the integrated DNA provirus is transcribed into mRNA, which is then spliced into
smaller pieces. These small pieces are exported from the nucleus into the cytoplasm, where they are translated
into the regulatory proteins Tat (which encourages new virus production) and Rev. As the newly produced Rev
protein accumulates in the nucleus, it binds to viral mRNAs and allows unspliced RNAs to leave the nucleus,
where they are otherwise retained until spliced.[45] At this stage, the structural proteins Gag and Env are
produced from the full-length mRNA. The full-length RNA is actually the virus genome; it binds to the Gag
protein and is packaged into new virus particles.
HIV-1 and HIV-2 appear to package their RNA differently; HIV-1 will bind to any appropriate RNA, whereas
HIV-2 will preferentially bind to the mRNA that was used to create
the Gag protein itself. This may mean that HIV-1 is better able to
mutate (HIV-1 infection progresses to AIDS faster than HIV-2
infection and is responsible for the majority of global infections).
Recombination
Two RNA genomes are encapsidated in each HIV-1 particle (see
Structure and genome of HIV). Upon infection and replicationcatalyzed by reverse transcriptase, recombination between the two
genomes can occur.[46][47] Recombination occurs as the single-strand
(+)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. From 2 to 20 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.[47]
Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-
retroviral therapy.[48] 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. [49]
Bonhoeffer et al.[50] suggested that template switching by the reverse transcriptase acts as a repair process to
deal with breaks in the ssRNA genome. In addition, Hu and Temin[46] 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 ssRNA 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 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.[50]
HIV-1 infection causes chronic ongoing inflammation and production of reactive oxygen species. [51] Thus, the
HIV genome may be vulnerable to oxidative damages, including breaks in the single-stranded RNA. For HIV,
as well as for viruses generally, successful infection depends on overcoming host defensive strategies that often
include production of genome-damaging reactive oxygen. Thus, Michod et al.[52] suggested that recombination by viruses is an adaptation for repair of genome damages, and that recombinational variation is a byproduct that
may provide a separate benefit.
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