The Relationship between AIDS and HIV
June 7, 2000
Retrovirus HypothesisBy 1983, several research groups had focused on retroviruses for clues to the cause of AIDS (Gallo and Montagnier, 1987). Two recently recognized retroviruses, HTLV-I and HTLV-II, were the only viruses then known to preferentially infect helper T lymphocytes, the cells depleted in people with AIDS (Gallo and Reitz, 1982; Popovic et al., 1984). The pattern of HTLV transmission was similar to that seen among AIDS patients: HTLV was transmitted by sexual contact, from mother to child or by exposure to infected blood (Essex, 1982; Gallo and Reitz, 1982). In addition, HTLV-I was known to cause mild immunosuppression, and a related retrovirus, the lymphotropic feline leukemia virus (FeLV), caused lethal immunosuppression in cats (Essex et al., 1975).
In May 1983, the first report providing experimental evidence for an association between a retrovirus and AIDS was published (Barre-Sinoussi et al., 1983). After finding antibodies cross-reactive with HTLV-I in a homosexual patient with lymphadenopathy, a group led by Dr. Luc Montagnier isolated a previously unrecognized virus containing reverse transcriptase that was cytopathic for cord-blood lymphocytes (Barre-Sinoussi et al., 1983). This virus later became known as lymphadenopathy-associated virus (LAV). The French group subsequently reported that LAV was tropic for T-helper cells, in which it grew to substantial titers and caused cell death (Klatzmann et al., 1984a; Montagnier et al., 1984).
In 1984, a considerable amount of new data added to the evidence for a retroviral etiology for AIDS. Researchers at the National Institutes of Health reported the isolation of a cytopathic T-lymphotropic virus from 48 different people, including 18 of 21 with pre-AIDS, three of four clinically normal mothers of children with AIDS, 26 of 72 children and adults with AIDS, and one (who later developed AIDS) of 22 healthy homosexuals (Gallo et al., 1984). The virus, named HTLV-III, could not be found in 115 healthy heterosexual subjects.
Antibodies reactive with HTLV-III antigens were found in serum samples of 88 percent of 48 patients with AIDS, 79 percent of 14 homosexuals with pre-AIDS, and fewer than 1 percent of hundreds of healthy heterosexuals (Sarngadharan et al., 1984).
Shortly thereafter, the researchers found that 100 percent (34 of 34) of AIDS patients tested were positive for HTLV-III antibodies in a study in which none of 14 controls had antibodies (Safai et al., 1984b).
In a study in the United Kingdom reported later that year, investigators found that 30 of 31 AIDS patients tested were seropositive for HTLV-III antibodies, as were 110 of 124 individuals with persistent generalized lymphadenopathy (Cheingsong-Popov et al., 1984). None of more than 1,000 blood donors selected randomly had antibodies to HTLV-III in this study.
During the same time period, HTLV-III was isolated from the semen of patients with AIDS (Zagury et al., 1984, Ho et al., 1984), findings consistent with the epidemiologic data demonstrating AIDS transmission via sexual contact.
Researchers in San Francisco subsequently reported the isolation of a retrovirus they named the AIDS-associated retrovirus (ARV) from AIDS patients in different risk groups, as well as from asymptomatic people from AIDS risk groups (Levy et al., 1984). The researchers isolated ARV from 27 of 55 patients with AIDS or lymphadenopathy syndrome; they detected antibodies to ARV in 90 percent of 113 individuals with the same conditions. Like HTLV-III and LAV, ARV grew substantially in peripheral blood mononuclear cells and killed CD4+ T cells. The same group subsequently isolated ARV from genital secretions of women with antibodies to the virus, data consistent with the observation that men could contract AIDS following contact with a woman infected with the virus (Wofsy et al., 1986).
During the same period, HTLV-III and ARV were isolated from the brains of children and adults with AIDS-associated encephalopathy, which suggested a role for these viruses in the central nervous system disorders seen in many patients with AIDS (Levy et al., 1985; Ho et al., 1985).
By 1985, analyses of the nucleotide sequences of HTLV-III, LAV and ARV demonstrated that the three viruses belonged to the same retroviral family and were strikingly similar (Wain-Hobson et al., 1985; Ratner et al., 1985; Sanchez-Pescador et al., 1985). In 1986, the International Committee of Viral Taxonomy renamed the viruses the human immunodeficiency virus (HIV) (Coffin et al., 1986).
This article was provided by U.S. National Institute of Allergy and Infectious Diseases.