Antigenic variation of primate lentiviruses in humans and experimentally infected macaques

Neutralizing antibodies in primate lentivirus infections closely parallel the pathogenic process. Fast progression to disease is concomitant with lack of neutralizing antibodies to autologous virus. Slow or no progression to disease is linked with production of neutralizing antibodies to autologous virus. Moreover, there is evidence from the monkey model that the extent to which neutralizing antibodies cross-react may also be linked with the pathogenic process. Accordingly, slow progression to disease is associated with the capacity to neutralize several isolates and, conversely, fast progressors neutralize single autologous isolates, if any at all. In humans, transmission of HIV-1 from mother to child occurs more frequently in absence of autologous and/or heterologous neutralizing antibodies to primary isolates. Thus there is evidence that virus neutralization-perhaps in concert with the biological properties of the virus-is an important factor in primate lentivirus pathogenesis and transmission. Open questions are i) the extent of heterologous neutralization in slow or nonprogressor HIV-1- and HIV-2-infected individuals, ii) role of neutralizing antibodies in sexual transmission, and iii) what governs the specificity, broad or narrow, of the neutralizing antibody response in different hosts. If we can answer these questions we may be able to design preventive measures against HIV infection and/or disease. Studies on the interaction of virus and immune system in the infected host may therefore not only teach us about the pathogenetic process, but also help in developing an HIV vaccine.