Replication and pathogenesis of the AIDS virus.

Some of the major features of the acquired immune deficiency syndrome may be understood in terms of the characteristics of the virus. Life-long infection is a consequence of the life cycle of retroviruses, the formation of stably integrated viral genetic information into host-cell DNA. The silent infection, controlled replication, and profile replication may be understood in terms of the interactions of the positive and negative regulatory genes that control virus growth. Selective infectivity and selective cytotoxicity of HIV-1 are primarily the consequences of the properties of the envelope glycoprotein and its interactions with the surface CD4 molecule. The ability of HIV-1 to enter a state of prolific replication in the presence of an antiviral immune response is largely attributed to the design of the outside of the virus. The functional domains of the envelope glycoprotein are not accessible to the immune system and other regions appear to be covered by a dense cloud of sugar molecules. Concealment of the virus by regulated growth, by budding to the interior surfaces of macrophages as well as concealment by a sugar coating, may help to explain the failure to protect chimpanzees from infection by candidate vaccines. Rapid medical prophylaxis is required in populations that currently experience high incidence of HIV-1 infection. Chemoprevention, the use of chemicals to prevent establishment of viral infection, in addition to vaccination should be investigated as means to control the AIDS epidemic.