What makes HIV lethal
aids-causing human immunodeficiency virus (hiv) is unusually lethal when compared to similar viruses like the simian immunodeficiency virus (siv). According to a new us study, the reason for the difference may be the loss of a gene function during viral evolution.
siv is commonly found among monkeys; but infected non-human primates usually do not develop aids. Researchers led by Frank Kirchhoff of the University of Pennsylvania, Philadelphia, found that this may be because of the presence of a viral protein called nef. Besides helping sivs to multiply efficiently, nef also slows down the growth of critical agents of immunity called t cells in the host. On the other hand, the nef protein produced by hiv-1, the more virulent of the two forms of hiv ( the other being hiv-2), accelerates t cell production. But all the t cells produced are killed by hiv-1, which exhausts the immune system and leaves the body vulnerable to bacteria, other viruses and microbes. The findings were published in the journal Cell (Vol 125, No 6, June 16, 2006).
There are more than 30 siv s, whose molecular structure is known and all of them encode a nef gene. The researchers found that nef variants in the majority of primate siv s, including the less virulent human strain hiv-2, suppress the expression of a receptor found on the surface of t cells, thus making the immune cells less responsive to activation. In contrast, the nef gene of hiv-1 failed to limit t cell activation and their death.
"The findings suggest that the gene function was lost during viral evolution in a lineage that gave rise to hiv-1 and may have predisposed the simian precursor of hiv-1 for greater pathogenicity in humans," says Kirchhoff.
The observed difference in nef function may provide -- for the first time -- a mechanism to explain why several monkey species naturally infected with siv do not develop aids -like symptoms. According to the researchers the results also hint at the possibility of treatments that could carefully limit the immune system in infected humans.
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