The HIV virus infects its host cells (T cells) by binding to a receptor on these
ID: 66180 • Letter: T
Question
The HIV virus infects its host cells (T cells) by binding to a receptor on these cells called CCR5. AIDS, caused by HIV, is an endemic disease in some countries like Botswana where about 30% of people are infected with the virus. However, even in countries like Botswana, scientists realized that some families were never infected with the HIV virus. To determine why these people never got infected, the scientists determined the DNA sequence of the CCR5 gene in families who never were infected, and other individuals who were infected: When they completed this analysis they found that the CCR5 gene differed by a single nucleotide between these two groups. How do you think this single nucleotide difference could be protecting these individuals from HIV? Would you expect the protected individuals to be homozygous or heterozygous for this SNP? Please explain your logic briefly.Explanation / Answer
a) HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals.
The CD14 C-260T T-allele in 56% of the cohort and evidence of subclinical atherosclerosis in 27%. TT genotype was associated with higher sCD163 (p = 0.009) but only marginally higher sCD14 (p = 0.209) and no difference in hsCRP (p = 0.296) compared to CC/CT. In multivariable analysis, only Framingham risk score was independently associated with higher cIMT while lower sCD163 was trending towards significance. No association was found in TT-genotype carriers and cIMT measurements.
b) the influence of CD14 C-260T SNP on markers of monocyte activation and systemic inflammation. There was no significant difference in the concentration of sCD14 between CC/CT vs TT genotype carriers (p=0.266) but TT genotype carriers had significantly higher sCD163 levels compared to CC/CT carriers (p=0.008). The associations did not change when controlling for the effects of smoking, current CD4 T-cell counts, age and gender, factors previously shown to strongly influence monocyte/macrophage activation levels. There was no significant difference in the median concentration of hsCRP in the two groups, however hsCRP was significantly correlated with levels of sCD14 (p=0.030) and sCD163 (p=0.022). These associations remained unchanged when analysis was done using a recessive model
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