Pathogenesis of HIV and SIV

Infections by viruses of the lentivirus genus, most notably human immunodeficiency virus type 1 (HIV-1), are characterized by remarkably complex interactions with the host and a chronic course of disease. Common features of diseases caused by lentiviruses include long and variable incubation periods, persistent viral replication, neurologic manifestations, and destruction of specific hematologic or immunologic cells (Desrosiers and Letvin 1987); some of these characteristics, particularly as they relate to nonprimate lentiviruses, are described in Chapter 10 All lentiviruses exhibit a common morphogenesis and morphology, a tropism for macrophages, extensive genetic and antigenic variability, and the presence of additional regulatory genes not found in other groups of retroviruses. Lentiviruses are not directly oncogenic, although the immune disorders they induce often permit the growth of certain neoplasms, such as lymphomas and Kaposi's sarcoma.

Lentiviruses have been isolated from several animal species including sheep, goats, horses, cattle, cats, monkeys, and humans. HIV-1 and HIV-2 are the only known human lentiviruses. Infection of humans with HIV-1 causes a dramatic decline in the number of CD4⁺ T lymphocytes. When the number of these cells becomes low enough, opportunistic infections and neoplasms occur. Neurologic abnormalities, which occur in a majority of HIV-infected individuals, can be observed in the absence of other clinical manifestations (Fauci 1988). The HIV-related lentiviruses of nonhuman primates are collectively called simian immunodeficiency viruses (SIVs). Related but distinct SIVs have been isolated from several species of African monkeys. SIV and HIV will be referred to as primate lentiviruses; more distant relatives from other animal species will be referred to as nonprimate lentiviruses. As with HIV, infection of an appropriate host with SIV results in the decline of the absolute number of CD4⁺ T cells, an inversion of the CD4/CD8 T-cell ratio, neurologic abnormalities, and opportunistic infections (Simon et al. 1994).

Nonprimate lentiviruses have been isolated from a wide variety of mammals and cause a variety of diseases. Bovine immunodeficiency virus (BIV), a lentivirus isolated from the leukocytes of cattle, produces persistent lymphocytosis, lymphadenopathy, and central nervous system lesions. Feline immunodeficiency virus (FIV) is a lymphotropic lentivirus that causes generalized lymphadenopathy and susceptibility to opportunistic infections. The equine infectious anemia virus (EIAV) is unique among the lentiviruses in that it causes in infected horses periodic, recurrent episodes of fever, hemolytic anemia, and immunologic disorders. The caprine arthritis-encephalitis virus (CAEV) causes a progressive leukoencephalomyelitis that ultimately ends in paralysis and death. In some goats, persistent infection with CAEV is associated with synovitis, periarthritis, and chronic progressive pneumonia. Maedi/visna virus (MVV), a lentivirus of sheep, causes a chronic, progressive, interstitial pneumonia and severe demyelinating encephalitis. These agents are discussed in greater detail in Chapter 10; this chapter concentrates on the pathogenesis caused by infection with HIV and closely related primate lentiviruses.