HOST FACTORS IN THE PATHOGENESIS OF HIV-DISEASE

Host factors play an important role in determining rates of disease pr ogression in human immunodeficiency virus (HIV)-infected individuals. HIV is able to subvert the host immune system by infecting CD4(+) T ce lls that normally orchestrate immune responses and by inducing the sec retion of proinflammatory cytokines that the virus can utilize to its own replicative advantage. The recognition that certain chemokine rece ptors serve as necessary co-factors for MV entry into its target cells as well as the fact that ligands for these receptors can modulate the efficiency of HN infection has expanded the number and scope of host factors that may impact the pathogenesis of HIV disease. This area of investigation will no doubt yield novel therapeutic strategies for int ervention in HIV disease; however, caution is warranted in light of th e enormous complexity of the pleiotropic cytokine and chemokine networ ks and the uncertainty inherent in manipulating these systems. HIV-inf ected long-term non-progressors represent an excellent model to study potential host factors involved in HN disease pathogenesis. Genetic fa ctors certainly have a major impact on the immune responses mounted by the host. In this regard, a polymorphism in the gene for the HIV co-r eceptor CC chemokine receptor 5 (CCR5), which serves as a coreceptor f or macrophage (M)-tropic strains of HIV, affords a high degree of prot ection against HIV infection in individuals homozygous for the genetic defect and some degree of protection against disease progression in H IV-infected heterozygotes. HIV-specific immune responses, including cy totoxic T-lymphocyte (CTL) responses and neutralizing antibody respons es, also appear to play salutary roles in protecting against disease p rogression.