The Lentiviruses are complex Retroviruses whose core is cone shaped in the mature virion. The most important are the Human Immunodeficiency Viruses, HIV-1 and HIV-2. Other members of the genus include Simian Immunodeficiency Virus (SIV), Feline Immunodeficiency Virus (FIV), Bovine Ficiency Virus (BIV), Visna virus (which causes disease in sheep), Equine Infectious Anemia virus (EIAV), and Caprine Arthritis-Encephalitis Virus (CAEV). As described above, the regulation of Lentivirus replication is complex because Lentiviruses encode three to six accessory genes, depending on the virus, to regulate the replication cycle and aid in the assembly of progeny viruses.

All Lentiviruses have a specific tropism for macrophages, which comprise the major reservoir of infected cells in an animal. Other cells can also be infected and this can be important in the disease process (e.g., CD4+ T cells in HIV infection). Lentiviruses establish a lifelong, chronic infection which elicits a vigorous immune response that is still unable to clear the infection. Most known Lentiviruses cause serious disease in their native host after a long latent period. However, SIV produces a asymptomatic, lifelong infection of its natural host, African monkeys. Intriguingly, SIV causes AIDS when transmitted to Asian monkeys.