May 16, 2003 (Journal of Clinical Investigation) -- A genetic mutation in a human immunodeficiency virus (HIV) protein may help explain why a small proportion of people infected with HIV remain healthy for over a decade or more, while others ultimately develop AIDS.
Andrew Badley and colleagues from the Mayo Clinic in Rochester, Minnesota, report their findings in the May 15, 2003 issue of the Journal of Clinical Investigation.
The diverse group of long-term, healthy, HIV-infected individuals, known as "long-term nonprogressors" is defined by infection with HIV for seven years or more, with no history of HIV-related symptoms, no exposure to antiretroviral drug therapy, and preserved immune function - in particular, a high level of CD4+ T cells.
Dr. Badley and his fellow investigators, interested in determining the specific factors that protect these individuals from HIV disease progression, have found that a mutation in the HIV-1 viral protein (Vpr) is more commonly found among HIV isolates from long-term nonprogressors than among isolates from patients with progressive disease. Vpr suppresses proliferation of host CD4+ T cells - first line defenders in the host immune response - and also produces signals that cause the death of both infected and uninfected host cells (via a process called apoptosis). The researchers demonstrate that patients with progressive HIV disease have high levels of apoptosis, while patients with nonprogressive HIV disease have levels of apoptosis similar to those of uninfected individuals.
"These observations suggest that Vpr plays a significant role in CD4+ T cell depletion in individuals infected with HIV. Moreover, it suggests a therapeutic opportunity for the development of Vpr inhibitors to reduce T cell death during HIV infection" states Dr. Badley.
"Based on these findings, several tantalizing possibilities arise" writes Dr. Guido Kroemer from the Universitι de Versailles, France in his accompanying commentary. "Vpr inhibitors may be expected to have a positive impact on the prognosis of HIV-1 infection, provided that Vpr is truly important for AIDS pathogenesis".
