hiv - everything you need to know 6

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11/15/13 HIV - Wi k i pedi a, the fr ee ency cl opedi a en.wikipedia.org/w iki /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  prot ei n accu m u l ates i n th e n u cl eu s, i t binds to v i ral m RNA s an d al l ows u n spl i ced R NAs t o l eav e th e n u cleus, where they are otherwise retained until spliced. [45]  At this stage, the structural proteins Gag and Env are  produ ced f rom th e f u l l -le n g th m RNA . Th e f u l l -l en g th RNA i s act u al l y th e v i ru s g en om e; i t bi n ds to t h e Gag  prot ei n an d i s packag ed i n to n ew v i ru s par ti cl es. 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 replication catalyzed 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  betw een th e tw o copi es of th e v i ral RNA . Th i s f orm of recom bi n ati on 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 therap y. [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  ben ef i t of repai r can occu r at e ach repl i cati on cy cl e, an d th at t h i s ben ef i t can be real i z ed wh eth er or n ot th e tw o 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 v i ru ses i s an adapta ti on f or r epai r of g en om e dam ag es, an d th at re com bi n ati on al v ari ati on i s a by produ ct t h at may provide a separate benefit.

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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.