The transition from HIV infection to AIDS is variable among infected people, ranging from a few years after initial infection to living symptom-free for 20 or more years, as in so-called long-term non progressors. Scientists have long understood that some genetic factors influence these differences, but hypothesize that other genetic factors of HIV progression may remain as yet undiscovered. VIDI affiliate investigator Dr. Pierre-Yves Bochud, along with VIDI co-director Dr. Julie McElrath and former PhD student Dr. Samuel Pine, studied the correlation of HIV progression with genetic variations in the genes coding for a family of proteins called toll-like receptors, and found two genetic variants associated with viral load levels early in infection – an early indicator of how disease may progress.
Toll-like receptors, or TLRs, sit on the surfaces of immune cells and act as flag-posts to alert the immune system to the presence of a variety of pathogens. Some TLRs are known to have interactions with HIV. Bochud and colleagues took blood samples from HIV positive volunteers in Seattle, and looked at their genetic variations in four TLR genes as well as the clinical features of HIV to AIDS. They found single nucleotide changes in 2 TLR genes (one in TLR4 and one in TLR9) that each correlated with different patterns of viral load. The TLR9 nucleotide change associated with lower viral load had been previously associated with slower progression to AIDS. These findings identify new players in the genetic mix of HIV progression.
Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals. Pine SO, McElrath MJ, Bochud PY. AIDS. 2009 Nov 27;23(18):2387-95.