HIV heterogeneity and viral pathogenesis

HIV research in the past year has elucidated many questions relevant to strategies for treatment and control. For instance, there is a greater understanding of the diversity of HIV isolates as well as the wide range of potential cells sensitive to infection. The search for a safe, effective vaccine now calls for more caution in the light of the discovery of neutralization-resistant variants and antibody-mediated enhancement of infection. Efforts to control HIV must take into account the various mechanisms of virus entry into host cells, and the processes involved in cytopathic effects. Moreover, the role of cells of the mononuclear phagocyte system as reservoirs for HIV particles should be recognized. Together with new information about cytokine induction of HIV, the concept of latent infection of monocytes and macrophages has profound implications for virus persistence and dissemination, especially in the seronegative individual. While many factors about HIV have been uncovered in the past year, several questions remain unanswered and new ones have arisen. For instance, in how many ways does the virus kill in host cell? What causes latency and why does it occur in some but not all hosts? How can virus-filled macrophage vesicles be reached by therapeutic agents or prevented from releasing HIV? What surveillance mechanisms allow some productively infected hosts (cells as well as individuals) to survive beyond expectation? These and other questions should provoke future research on this presently complex and challenging pathogen.