Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity, the determinants of cell-mediated immunity in humans are poorly understood. A new paper demonstrates that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence cell-mediated immunity in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered cell-mediated immunity in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and cell-mediated immunity. These results identify CCL3L1 and CCR5 as major determinants of cell-mediated immunity and demonstrate that these host factors influence HIV pathogenesis through their effects on both cell-mediated immunity and other virus entry-independent mechanisms.
Virus load – the concentration of HIV virus in the blood – is believed to be a major predictor of how an HIV-infected person will fare in the battle against developing AIDS. But this new research suggests that individual variations in cell-mediated immunity may be almost as important. Approximately 6% of the variability in disease progression between individuals comes from these genes influence on cell-mediated immunity. One of the researchers, Matthew Dolan at the Wilford Hall United States Air Force Medical Center in San Antonio, said:
“Some will do well and some will do poorly. And some of that is preordained before people get infected.”