Indian HIV strains do not need to switch over to a coreceptor (a second cell surface required for the entry of a pathogen into a host) as disease progresses, unlike their western counterparts, new research suggests1. In western studies a switch from utilization of the CCR5 to CXCR4 coreceptor has been linked to faster disease progression.
HIV infection is initiated by the chemokine receptor CCR5 (R5 strains). While in the West, about 50% of these strains switch over to the coreceptor CXCR4 (X4 strains) as disease progresses, in India and large parts of Africa the virus remains with R5 throughout asymptomatic infection and disease.
The CCR5 protein is present on macrophages and dendritic cells and on activated T cells. The CXCR4 protein is present on resting T cells. While HIV can infect both types of T cells, virus replicates more efficiently in activated T cells.
"The first issue is that uninfected people in India and Africa show higher numbers of CCR5-positive CD4 T cells compared to those living in the West," says Shahid Jameel, one of the key investigators.
Similar findings were earlier reported2 by a group from Christian Medical College in Vellore.
One hypothesis on why this happens is that people in India and Africa are exposed to a higher burden of other infections and therefore have higher numbers of activated T cells to fight off those infections. This is exploited by HIV. Since there are plenty of CCR5+CD4 cells, there is no evolutionary pressure on the virus to change its coreceptor utilization phenotype.
The researchers found that activated CD4 T cells in HIV-infected Indians showed downregulation of CCR5. This was opposite to that observed in Western patients, but similar to the observation in Africans. "Our marker for activation here was not CCR5, but another molecule called HLADR that is expressed only on activated CD4 T cells", Jameel adds.
The team is hoping these findings will form the basis of future explorations.
