Repository logo
 

APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4R T-cell counts and plasma viral load.

Simple item page
dc.contributor.authorReddy, Kavidha.
dc.contributor.authorWinkler, Cheryl Ann.
dc.contributor.authorWerner, Lise.
dc.contributor.authorMlisana, Koleka Patience.
dc.contributor.authorAbdool Karim, Salim Safurdeen.
dc.contributor.authorNdung'u, Peter Thumbi.
dc.date.accessioned2012-11-28T13:39:37Z
dc.date.available2012-11-28T13:39:37Z
dc.date.created2008
dc.date.issued2008
dc.description.abstractObjectives: 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. Methods: 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. Results: 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. Conclusion: 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.en
dc.identifier.citationReddy, K. et al. 2010. APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4R T-cell counts and plasma viral load. Aids 24, pp. 195-204.en
dc.identifier.issn0269-9370
dc.identifier.urihttp://dx.doi.org/10.1097/QAD.0b013e3283353bbaen
dc.identifier.urihttp://hdl.handle.net/10413/8036
dc.language.isoenen
dc.publisherLippincott Williams & Wilkins.en
dc.subjectHIV infections--Virology.en
dc.subjectHIV (Viruses)en
dc.titleAPOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4R T-cell counts and plasma viral load.en
dc.typePeer reviewed journal articleen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Reddy_Kavidha_2008.pdf
Size:
478.5 KB
Format:
Adobe Portable Document Format
Description:
Journal article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.64 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Research papers (Caprisa)