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APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load.

ABSTRACT: In the absence of HIV-1 virion infectivity factor (Vif), cellular cytosine deaminases such as apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) inhibit the virus by inducing hypermutations on viral DNA, among other mechanisms of action. We investigated the association of APOBEC3G mRNA levels and genetic variants on HIV-1 susceptibility, and early disease pathogenesis using viral load and CD4 T-cell counts as outcomes.Study participants were 250 South African women at high risk for HIV-1 subtype C infection. We used real-time PCR to measure the expression of APOBEC3G in HIV-negative and HIV-positive primary infection samples. APOBEC3G variants were identified by DNA re-sequencing and TaqMan genotyping.We found no correlation between APOBEC3G expression levels and plasma viral loads (r = 0.053, P = 0.596) or CD4 T-cell counts (r = 0.030, P = 0.762) in 32 seroconverters. APOBEC3G expression levels were higher in HIV-negative individuals as compared with HIV-positive individuals (P < 0.0001), including matched pre and postinfection samples from the same individuals (n = 13, P < 0.0001). Twenty-four single nucleotide polymorphisms, including eight novel, were identified within APOBEC3G by re-sequencing and genotyping. The H186R mutation, a codon-changing variant in exon 4, and a 3' extragenic mutation (rs35228531) were associated with high viral loads (P = 0.0097 and P < 0.0001) and decreased CD4 T-cell levels (P = 0.0081 and P < 0.0001), respectively.These data suggest that APOBEC3G transcription is rapidly downregulated upon HIV-1 infection. During primary infection, APOBEC3G expression levels in peripheral blood mononuclear cells do not correlate with viral loads or CD4 T-cell counts. Genetic variation of APOBEC3G may significantly affect early HIV-1 pathogenesis, although the mechanism remains unclear and warrants further investigation.

SUBMITTER: Reddy K

PROVIDER: S-EPMC3470914 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load.

Reddy Kavidha K Winkler Cheryl A CA Werner Lise L Mlisana Koleka K Abdool Karim Salim S SS Ndung'u Thumbi T

AIDS (London, England) 20100101 2

<h4>Objectives</h4>In the absence of HIV-1 virion infectivity factor (Vif), cellular cytosine deaminases such as apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) inhibit the virus by inducing hypermutations on viral DNA, among other mechanisms of action. We investigated the association of APOBEC3G mRNA levels and genetic variants on HIV-1 susceptibility, and early disease pathogenesis using viral load and CD4 T-cell counts as outcomes.<h4>Methods</h4>Study participan ...[more]

PMID: 19996938

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APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load.

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APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load.

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