2005 Fiscal Year Final Research Report Summary
Host genetic polymorphisms that can affect HIV diseases.
| Project/Area Number |
14021056
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
SHIODA Tatsuo Osaka University, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (00187329)
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| Project Period (FY) |
2002 – 2005
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| Keywords | HIV-1 / chemokine / chemokine receptor / cytokine, genetic / polymorphism / disease progression |
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| Research Abstract |
1. CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide deletion mutation which is observed exclusively in Asians. We found that the CCR5-893(-) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1 transmission and disease progression.
2. A valine to isoleucine substitution at position 64 of CCR2 (CCR2-64I) is associated with a delay in progression to AIDS in HIV-1-infected individuals. Our results suggest that an A isoform of CCR2 (CCR2A) binds to CCR5 in the cytoplasm and down-modulates its surface expression. We propose that the increased ability of CCR2A-64I to down-modulate CCR5 expression might be a possible cause of a delay in HIV-1 disease progression in patients with this allele.
3. The interleukin (IL)-4-589T allele bears a single nucleotide polymorphism at position・89 upstream from the open-reading frame of the IL-4 gene. Serum virus load was lower in patients with IL-4-589T than in those without this allele (P=0.02) in the French SEROCO cohort. Kaplan-Meier analysis survival curves showed a slower progression to clinical AIDS in carriers of IL-4-589T (P=0.04). These results suggest that IL-4-589T protects against HIV-1 disease progression by reducing virus load.
4. A total of 246 Thai female samples were genotyped for IL4 and RANTES promoter polymorphisms by PCR-RFLP. Our results implicate the significant protective effect of IL4-589T and RANTES-28G on HIV disease progression in Thais. In contrast, RANTES In1.1C without RANTES-28G had an accelerating effect on HIV disease progression.
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