HIV-1's High Virulence Might Be An Accident Of Evolution

The virulence characteristic of HIV-1--the virus predominantly responsible for human AIDS--might amount to an accident of evolution, new evidence reveals. A gene function lost during the course of viral evolution predisposed HIV-1 to spur the fatal immune system failures that are the hallmarks of AIDS, researchers report in the June 16, 2006 Cell.

AIDS has killed more than 25 million people since it was first recognized in 1981, according to The Joint United Nations Programme on HIV and AIDS. In 2005, an estimated 4.1 million were newly infected with the virus. While infection with related strains of "simian immunodeficiency virus" (SIV) is similarly rampant among many species of monkeys, naturally infected nonhuman primates usually don't suffer the symptoms associated with AIDS. The evidence now revealed by an international team of researchers is the first to offer an explanation for this striking difference.

The group found that a viral protein earlier shown to help the virus evade the immune system, thereby allowing the SIVs that infect monkeys to persist and multiply with high efficiency, also has a protective role in the host immune system. The viral Nef protein ratchets down the activation of critical agents of immunity called T cells following SIV infection, thereby limiting the detrimental effects otherwise caused by chronically strong immune activation.

The HIV-1 Nef protein, and those of its closest related simian viruses, however, lack this protective function, leaving those infected susceptible to the heightened immune activation associated with progression to full-blown AIDS, reports Frank Kirchhoff of the University of Ulm in Germany and his colleagues.

"Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses that likely evolved to maintain viral persistence in the context of an intact host immune system," the researchers said. "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."