Cytokine regulation of HIV expression

Infection with the human immunodeficiency virus (HIV) is characterized by a long and variable asymptomatic phase followed by the development of the acquired immunodeficiency syndrome (AIDS) in a substantial proportion of individuals within 10 years. An understanding of the mechanism by which the infection progresses in vivo to an ultimate destruction of the immune system is essential to the design of rational approaches to anti-viral therapy, immune reconstitution, and vaccine development. To delineate these complex processes, we have established an in vitro model of latent or chronic HIV infection and have used this model to examine ways in which HIV replication can be upregulated. We have shown that cytokines are important mediators of HIV replication in chronically HIV-infected cells. Thus, the virus has incorporated itself into the human immune system and utilizes for its own propagation many of the cellular and molecular mechanisms which the immune system uses to maintain its homeostatic regulation. Studies in this area will not only shed important light on the immunopathogenesis of HIV, but will certainly lead to greater depth in our understanding of the normal function of the human immune system.