As a retrovirus, HIV is an RNA virus that codes for the enzyme reverse transcriptase, which transcribes the viral genomic RNA into a DNA copy that ultimately integrates into the host cell genome (Fauci, 1988). Within the retrovirus family, HIV is classified as a lentivirus, having genetic and morphologic similarities to animal lentiviruses such as those infecting cats (feline immunodeficiency virus), sheep (visna virus), goats (caprine arthritis-encephalitis virus), and non-human primates (simian immunodeficiency virus) (Stowring et al., 1979; Gonda et al., 1985; Haase, 1986; Temin, 1988, 1989). Like HIV in humans, these animal viruses primarily infect cells of the immune system, including T lymphocytes and macrophages (Haase, 1986, 1990; Levy, 1993) (Table 1).

Table 1. Lentiviruses

Virus	Host	Primary cell type infected	Clinical disorder
Equine infectious anemia virus (EIAV)	Horse	Macrophages	Cyclical infection in the first year: hemolytic anemia and sometimes encephalopathy
Visna virus	Sheep	Macrophages	Encephalopathy
Caprine arthritis-encephalitis virus (CAEV)	Goat	Macrophages	Immune deficiency, encephalopathy
Bovine immune deficiency virus (BIV)	Cow	Macrophages	Lymphadenopathy, lymphocytosis, CNS disease (?)
Feline immunodeficiency virus (FIV)	Cat	T lymphocytes	Immune deficiency
Simian immunodeficiency (SIV)	Primate	T lymphocytes	Immune deficiency, encephalopathy
Human immunodeficiency virus (HIV)	Human	T lymphocytes	Immune deficiency, encephalopathy

Reference: Levy, 1993.

Lentiviruses often cause immunodeficiency in their hosts in addition to slow, progressive wasting disorders, neurodegeneration and death (Haase, 1986, 1990). SIV, for example, infects several subspecies of macaque monkeys, causing diarrhea, wasting, CD4+ T cell depletion, opportunistic infections and death (Desrosiers, 1990; Fultz, 1993). HIV is closely related to SIV, as evidenced by viral protein cross-reactivity and genetic sequence similarities (Franchini et al., 1987; Hirsch et al., 1989; Desrosiers, 1990; Myers, 1992).

One feature that distinguishes lentiviruses from other retroviruses is the remarkable complexity of their viral genomes. Most retroviruses that are capable of replication contain only three genes--env, gag and pol (Varmus, 1988). HIV contains not only these essential genes but also the complex regulatory genes tat, rev, nef, and auxiliary genes vif, vpr and vpu (Greene, 1991). The actions of these additional genes probably contribute to the profound pathogenicity that differentiates HIV from many other retroviruses.

CD4+ T cells, the cells depleted in AIDS patients, are primary targets of HIV because of the affinity of the gp120 glycoprotein component of the viral envelope for the CD4 molecule (Dalgleish et al., 1984; Klatzmann et al., 1984b; McDougal et al., 1985a, 1986). These so-called T-helper cells coordinate a number of critical immunologic functions. The loss of these cells results in the progressive impairment of the immune system and is associated with a deteriorating clinical course (Pantaleo et al., 1993a). In advanced HIV disease, abnormalities of virtually every component of the immune system are evident (Fauci, 1993a; Pantaleo et al., 1993a).