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Association of CCR5 human haplogroup E with rapid HIV type 1 disease progression
Ming Li1, Ruiguang Song, Silvina Masciotra
1Division of AIDS, STD, and TB Laboratory Research, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Insights
Certain CCR5 human haplogroups (HH) impact HIV-1 disease progression. The HHE haplogroup was significantly more frequent in rapid HIV progressors, indicating its role in faster disease advancement.
Area of Science:
- Genetics
- Immunology
- Virology
Background:
- The CCR5 receptor plays a critical role in HIV-1 infection and pathogenesis.
- Genetic variations in CCR5, including single nucleotide polymorphisms (SNPs), define human haplogroups (HH).
- These CCR5 HH may influence individual susceptibility and disease progression following HIV-1 infection.
Purpose of the Study:
- To investigate the distribution of nine defined CCR5 human haplogroups (HHA-HHE, HHF*1, HHF*2, HHG*1, HHG*2).
- To examine the association between CCR5 HH and HIV infection status.
- To determine the correlation of CCR5 HH with HIV-1 disease progression, specifically rapid versus slow progression.
Main Methods:
- Genotyping of CCR5 regulatory, CCR2, and CCR5 coding regions to define CCR5 human haplogroups.
- Analysis of CCR5 HH distribution in HIV-seronegative and HIV-seropositive individuals.
- Survival analysis to assess the association of CCR5 HH with CD4 cell count decline.
Main Results:
- The frequency of the HHE haplogroup was similar between HIV-seronegative and HIV-seropositive groups.
- HHE frequency was significantly higher in rapid progressors (RP) compared to slow progressors (SP) (48.2% vs. 22.9%, p = 0.002).
- HHE heterozygosity and homozygosity were associated with accelerated CD4 cell count decline (adjusted RH 2.44, p = 0.045; adjusted RH = 3.12, p = 0.037, respectively).
Conclusions:
- CCR5 human haplogroups, particularly HHE, are associated with HIV-1 disease progression.
- The HHE haplogroup may serve as a genetic marker influencing the rate of CD4 cell count decline in HIV-infected individuals.
- These findings underscore the importance of CCR5 genetic variations in modulating HIV-1 pathogenesis.
Abstract:
The combination of unique single nucleotide polymorphisms in the CCR5 regulatory and in the CCR2 and CCR5 coding regions, defined nine CCR5 human haplogroups (HH): HHA-HHE, HHF*1, HHF*2, HHG*1, and HHG*2. Here we examined the distribution of CCR5 HH and their association with HIV infection and disease progression in 36 HIV-seronegative and 76 HIV-seropositive whites from North America and Spain [28 rapid progressors (RP) and 48 slow progressors (SP)]. Although analyses revealed that HHE frequencies were similar between HIV-seronegative and HIV-seropositive groups (25.0% vs. 32.2%, p > 0.05), HHE frequency in RP was significantly higher than that in SP (48.2% vs. 22.9%, p = 0.002). Survival analysis also showed that HHE heterozygous and homozygous were associated with an accelerated CD4 cell count decline to less than 200 cells/microL (adjusted RH 2.44, p = 0.045; adjusted RH = 3.12, p = 0.037, respectively). These data provide further evidence that CCR5 human haplogroups influence HIV-1 disease progression in HIV-infected persons.
