The Influence of Viral Factors on Long-term Nonprogressing HIV
Posted Oct 22 2008 4:32pm
The progression of HIV infection varies from one individual to another. Although “the median time from infection to development of AIDS is 8 to 10 years,” some individuals, known as long-term nonprogressors, fail to develop AIDS after infection with HIV (Hogan and Hammer, 2001). These individuals have been identified on various continents, and include persons with various types of exposure, such as commercial sex workers, hemophiliacs who have received HIV positive blood during transfusions, infants born to seropositive mothers, health care professionals accidentally infected by needlestick, intravenous drug users, and sexual partners of known HIV positive individuals (Zhu et al., 2002). Despite prolonged periods of HIV infection, long-term nonprogressors “remain asymptomatic and have normal CD4 cell counts and low or undetectable viral loads,” (Hogan and Hammer, 2001). The existence of long-term nonprogressors indicates the possibility of a natural immunity to HIV (Haynes et al., 1996). Though current research suggests a broad range of potential viral and host factors that may influence progression rates, further investigation is necessary to clarify the roles of each of these factors and elucidate how this knowledge can be applied to the therapeutic development of vaccines (Hogan and Hammer, 2001). This podcast will focus solely on the influence of viral factors. Research has indicated that certain characteristics of the HIV-1 virus may affect transmission and progression rates. These factors include viral tropism, viral escape, viral attenuation, and viral subtype. Two variants of viral tropism have been identified for the HIV-1 virus, which are macrophage-tropic (M tropic) and T-cell-tropic (T-tropic). Early HIV infection usually results from M-tropic strains. As the virus mutates, its phenotype may change, resulting in a T-tropic strain, which is known to increase the rate of T-cell depletion. The progression from one tropism to the other has been associated with increased pathogenicity and progressive disease (Connor and Ho, 1994). Another factor that has been linked to disease progression is viral escape from immune response. Viral escape may result from mutations that arise in the gag, pol, and env genes, allowing the virus to elude intense cell-mediated and humoral immune response (Hogan and Hammer, 2001). Additionally, attenuated HIV-1 viruses have been linked with slowed progression of AIDS infection. More specifically, a group of individuals infected with a strain of HIV-1 with a deletion in the nef gene have been identified. When discovered, all eight individuals infected with this strand of HIV-1 appeared to have nonprogressive infection. Upon tracking these individuals, however, the disease reflects slowed progression (Learmont et al., 1992). Further investigation into attenuated strains may present methods that can be used to delay progression of HIV-1 and prolong the lives of infected individuals. Finally, individuals with different viral subtypes may experience slowed or enhanced disease progression. Epidemiologic studies seeking differences between subtypes are difficult and often inconclusive. However, there is evidence suggesting that HIV-2, a related human retrovirus, is less virulent and less infective, supporting the notion that HIV subtypes may have differential risks associated with transmission and pathogenicity (Marlink et al., 1994). Although the role of viral factors has not led to conclusive evidence that slows the progression HIV infection to the development of AIDS, continued research of the virus and host may clarify key features of the disease that may aid in the development of vaccines or treatments that induce individuals to acquire the mutations that long-term nonprogressors have obtained naturally (Hammer and Hogan, 2001).
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Hogan, C.M. and Hammer, S.M. (2001). Host determinants in HIV infection and disease (Part 1: Cellular and humoral immune responses). Annals of Internal Medicine 134:761-776.
Learmont, J., Tindall, B., Evans, L., Cunningham, A., Cunningham, P., Wells, J., et al. (1992). Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. Lancet 340:863-867.
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