Variations in two key genes help determine how swiftly an individual infected with HIV progresses to AIDS, according to a new study. The finding challenges quarter-century-old wisdom that what chiefly drives the advance to AIDS is "viral load," the amount of HIV in the blood, whose relentless rise bludgeons the immune system, according to a study in the British journal Nature Immunology. Instead, the authors argue, the situation is more complex. An individual's genetic profile can greatly affect replication of the human immunodeficiency virus (HIV) as well as the body's response to the intruder.
Benign to lethal
The interaction between the virus and the immune system switches "an otherwise benign infection to a lethal one," they said. The genes in question are called CCR5 and CCL3L1, although other genes, still not fully explored, may also play a part. CCR5 controls a key receptor, or docking point, on the surface of the CD4 immune cell onto which HIV latches. CCL3L1, meanwhile, controls an immune system signalling molecule called a chemokine that prevents the virus attaching itself to the CCR5 receptor. Previous work has already established that certain genetic variants in CCR5 appear to give a shield against viral entry.
Disease progression
The viral load at the early stages of infection accounted for only nine percent of the difference in speed at which HIV-infected people progressed to AIDS. Just as important was the sort of combination of the two genes. "The genetic variations contribute nearly as much to the extent of inter-individual variability in AIDS progression rates as does HIV-1 viral load.
The CCR5-CCL3L1 profile also has an effect on the immune responses among healthy people, which suggest that this combination might play a role in how the body responds to other infectious diseases, the paper suggests. Similar research in the field of genetic variation and HIV has looked at differences among three genes that control signalling molecules called human leucocyte antigens (HLA), which tag an intruder for destruction by the immune system.
