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Innate immune mechanisms in limiting HIV-1 pathogenesis among South African adults and mother-infant pairs.

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dc.contributor.advisorCarr, William Henry.
dc.contributor.authorNdlovu, Bongiwe Goodness.
dc.date.accessioned2013-11-11T13:28:14Z
dc.date.available2013-11-11T13:28:14Z
dc.date.created2012
dc.date.issued2012
dc.descriptionThesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2012.en
dc.description.abstractThis study was conducted to investigate the role of natural killer cell surface receptors, KIRs and their cognate HLA ligands in preventing HIV-1 acquisition and disease progression in HIV-1 exposed infants. Using DBS stored for 8 years from 21 pregnant South African women we evaluated 3 methods of gDNA extraction with and without whole genome amplification (WGA) to characterize immune-related genes: IL-10, KIR and HLA class I. However, IL-10 SNP typing was only for testing the quality of gDNA. QIAamp DNA mini kit yielded the highest gDNA quality (p<0.05; Wilcoxon Signed Rank Test) with sufficient yield for subsequent analyses. In contrast, WGA was not reliable for SSP-PCR analysis of KIR2DL1, KIR2DS1, KIR2DL5, and KIR2DL3 or high resolution HLA genotyping using a sequence-based approach. A cohort of 370 infants; 124 HIV-1 perinatally infected, 120 exposed uninfected and 126 unexposed healthy infants was used for KIR and HLA genotyping. After adjustment for viral load and multiple comparisons, the frequency of HLA-Cw*04:01 allele was likely to be associated with susceptibility to mother-to-child acquisition of HIV-1 in exposed infected (EI) infants (p=0.05; Logistic Regression analysis). HLA-A*23:01 was likely to be associated with decreased CD4 T lymphocyte count in HIV-1 infected infants (p=0.01; ANOVA), whereas HLA-B*81 tended to be associated with higher CD4 T lymphocyte count (p=0.04, ANOVA). We speculate that HLA-Cw*04:01 interacts with KIR2DL1 and inhibit NK cell responses which predispose the infants to HIV-1 infection. KIR2DS1 and KIR2DL5 were both associated with faster HIV-1 disease progression. Identified protective HLA-class I alleles could be used to present viral epitopes to either NK cells via KIRs or CTLs and enhance immune activation which may promote resistance to HIV-1 infection.en
dc.identifier.urihttp://hdl.handle.net/10413/9971
dc.language.isoen_ZAen
dc.subjectHIV-positive persons--South Africa.en
dc.subjectHIV-positive women--South Africa.en
dc.subjectHIV-positive children--South Africa.en
dc.subjectHIV infections--Transmission--South Africa.en
dc.subjectAIDS (Disease) in infants--South Africa.en
dc.subjectImmunologic diseases in infants--South Africa.en
dc.subjectHuman immunogenetics--South Africa.en
dc.subjectTheses--Paediatrics and child health.en
dc.subjectTheses--Immunology.en
dc.titleInnate immune mechanisms in limiting HIV-1 pathogenesis among South African adults and mother-infant pairs.en
dc.typeThesisen

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