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Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response.

Sampathkumar R, Shadabi E, Luo M - Adv Virol (2012)

Bottom Line: As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2.Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences.The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9.

ABSTRACT
As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response.

No MeSH data available.


Related in: MedlinePlus

(a) Error-causing machinery involved in HIV-1 mutagenesis. (b) A schematic sketch of selection pressures acting on HIV-1. Note: ART drugs block is shown in grey colour to differentiate from others, as such drugs exert influence over HIV-1 indirectly in patients undergoing ART.
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fig3: (a) Error-causing machinery involved in HIV-1 mutagenesis. (b) A schematic sketch of selection pressures acting on HIV-1. Note: ART drugs block is shown in grey colour to differentiate from others, as such drugs exert influence over HIV-1 indirectly in patients undergoing ART.

Mentions: HIV-1, with its RNA genome, demonstrates significant genetic diversity due its high mutation rate. It has diversified itself to such an extent, through its ability to form “cloud” of variants or quasispecies, that there is no single wild-type strain. In vitro data have shown that RNA viruses generate nonhomogeneous genetic clones that are closely related but genetically diverse, which are known as quasispecies. This phenomenon, which aids viruses to persist in their host, possibly causing disease, is observed in other RNA viruses such as hepatitis C and influenza virus as well [28, 29]. The reverse transcriptase (RT) of HIV-1, which lacks 3′-5′ exonucleolytic proof-reading function, misincorporates 1 in 6900 and 1 in 5900 nucleotides polymerized on the RNA and DNA template, respectively, and hence accounts for larger proportion of mutations seen in HIV-1 [30]. It has been estimated that, after a single round of HIV-1 replication, under the assumption of absence of selection pressure, the resulting progeny viruses will have substitution, frameshift and deletions at 24%, 4%, and 2%, respectively [31]. It is interesting to note that 80% of heterosexual-mediated HIV-1 infections are due to productive infection by a single HIV-1 virion [32–34]. HIV-1 evolves at about 1% per year [35]. Given that HIV-1 faces selection pressures, a gamut of mutations has shaped its genome since its origin, which in turn, ensures its virulence at population level [36, 37], despite the fact that certain mutations in its conserved region impacts its fitness negatively [38]. Further, a recent study that utilized phylogenetic comparative approach revealed that viral genotype, as against the host genetic profile, largely determines the HIV set-point viral load and hence the virulence [39]. A schematic sketch of error-causing machinery involved in HIV-1 mutagenesis and a gamut of selection pressure acting on HIV-1 are provided in Figures 3(a) and 3(b), respectively.


Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response.

Sampathkumar R, Shadabi E, Luo M - Adv Virol (2012)

(a) Error-causing machinery involved in HIV-1 mutagenesis. (b) A schematic sketch of selection pressures acting on HIV-1. Note: ART drugs block is shown in grey colour to differentiate from others, as such drugs exert influence over HIV-1 indirectly in patients undergoing ART.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3361994&req=5

fig3: (a) Error-causing machinery involved in HIV-1 mutagenesis. (b) A schematic sketch of selection pressures acting on HIV-1. Note: ART drugs block is shown in grey colour to differentiate from others, as such drugs exert influence over HIV-1 indirectly in patients undergoing ART.
Mentions: HIV-1, with its RNA genome, demonstrates significant genetic diversity due its high mutation rate. It has diversified itself to such an extent, through its ability to form “cloud” of variants or quasispecies, that there is no single wild-type strain. In vitro data have shown that RNA viruses generate nonhomogeneous genetic clones that are closely related but genetically diverse, which are known as quasispecies. This phenomenon, which aids viruses to persist in their host, possibly causing disease, is observed in other RNA viruses such as hepatitis C and influenza virus as well [28, 29]. The reverse transcriptase (RT) of HIV-1, which lacks 3′-5′ exonucleolytic proof-reading function, misincorporates 1 in 6900 and 1 in 5900 nucleotides polymerized on the RNA and DNA template, respectively, and hence accounts for larger proportion of mutations seen in HIV-1 [30]. It has been estimated that, after a single round of HIV-1 replication, under the assumption of absence of selection pressure, the resulting progeny viruses will have substitution, frameshift and deletions at 24%, 4%, and 2%, respectively [31]. It is interesting to note that 80% of heterosexual-mediated HIV-1 infections are due to productive infection by a single HIV-1 virion [32–34]. HIV-1 evolves at about 1% per year [35]. Given that HIV-1 faces selection pressures, a gamut of mutations has shaped its genome since its origin, which in turn, ensures its virulence at population level [36, 37], despite the fact that certain mutations in its conserved region impacts its fitness negatively [38]. Further, a recent study that utilized phylogenetic comparative approach revealed that viral genotype, as against the host genetic profile, largely determines the HIV set-point viral load and hence the virulence [39]. A schematic sketch of error-causing machinery involved in HIV-1 mutagenesis and a gamut of selection pressure acting on HIV-1 are provided in Figures 3(a) and 3(b), respectively.

Bottom Line: As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2.Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences.The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9.

ABSTRACT
As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response.

No MeSH data available.


Related in: MedlinePlus