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Abstract
Analyses of Host genetic factors that modulate progression of HIV/SIV/AIDS in India
Banerjea A.1
Introduction: Chemokines, interleukins or chemokine receptors play an important part in viral entry, pathogenesis and progression. Mutations in these genes can modulate progression of HIV-1.Since HIV-1 is rapidly spreading in India, it is important to study the frequency of disease modifying mutations in various host genes.
Methods: chemokine genes were amplified by PCR and subjected to sequence analyses.
Results: CCR5delta32 mutation is very rare in North India (1 out of 100 normals, <1% -no homozygous mutation detected). CCR5 promoter haplotypes indicate preponderence of 59353 (T to C)and 59402 (G to A)and few cases of 59402 mutation (G to A). High incidence of SDF-1 (G to A) was obsereved in normal individuals with 5% homozygous. This mutation afforded no protection against HIV-1 infection/progression. All the monkeys tested showed a remarkable double transition (GG to AA) at the same untranslated region of SDF-1 as in humans. Three cellular proteins were identified that showed binding to this region. Unique promoter polymorphisms were observed in RANTES and MIP-1-alpha promoter. Interestingly, most of the disease modifying mutations were preserved in monkeys. Besides, moneys had unique insertions, deletions or mutations in CCR5, IL-10, MCP-1 and IL-4 promoters. All the three species of monkeys (rhesus, bonnet and marmosets) showed a a remarkable mutation in the middle of one of the two NFKb motifs in RANTES that are present in close tandem.In contrast to high degree of polymorphism that was observed in CCR5 promoter, CXCXR4 promoter mutations were very small and rare in monkeys and humans. How these mutations modulate the expression of chemokines and interleukins is currently underway.
Conclusions: The HIV-1 protective mutation -CCR5delta32 is extremely rare in India. SDF-1 mutation is quite common but shows no correlation with protection against HIV-1.The conservation of HIV-1 disease modifying mutations in monkeys provide us the unique opportunity to study its role in pathogenesis in molecular details.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
WePe8.9B01
Suggested Citation
" Banerjea A.
Analyses of Host genetic factors that modulate progression of HIV/SIV/AIDS in India.
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
WePe8.9B01"
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