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HIV-infected individuals progress toward AIDS despite the early elicitation of a specific immune response. Analysis of the isotypic distribution of HIV-specific antibodies appears of special interest for two reasons: first, isotypic diversity is partly under the control of antigen-specific T-helper cells, the very cells infected by HIV; second, isotype determines antibody functions, effector (neutralization, antibody-dependent complement, or cell-mediated cytotoxicity) as well as blocking functions. We have investigated by Western blot analysis the isotypic profile of the antibody response to HIV structural proteins (env, gag, pol) and to the nonstructural protein F (3' orf), which is absent from the virion and might primarily target infected cells. In 115 asymptomatic individuals, infected by sexual contact (homosexual men) or intravenously (hemophiliacs), the response to gag-products was polyisotypic, including IgM, IgG1, IgG3 and IgA; the response to F was more restricted (IgM, IgG1, IgA) and the response to env strikingly restricted to the IgG1 isotype, suggesting different regulatory mechanisms in the B-cell response to these proteins. The isotypic distribution was also influenced by the route of infection, IgG4 and IgE (gag-specific) being exclusively elicited in the hemophiliac group. Finally, observations of potential diagnostic interest were made in a limited number of at-risk individuals; these included the presence of gag- and pol-specific IgM or IgA in the absence of any HIV-specific IgG isotypes; and the presence of gag- and F-specific antibodies in the absence of env-specific antibodies, suggesting the early occurrence of both isotypic and antigenic selection mechanisms during the course of HIV infection.

The neutralization properties of three independent HIV-2 isolates were examined in comparison with four diverse HIV-1 strains. Human sera containing antibodies specific to HIV-2 can cross-neutralize HIV-1. By contrast, HIV-1 sera are group-specific and have no neutralizing effect on HIV-2. Therefore, HIV-2 antigens may be important components for the development of broadly cross-protective AIDS vaccines.

To investigate transmission of lymphadenopathy-associated virus (LAV)/human T lymphotropic virus type III (HTLV-III) in long-term sexual partners, and the relationship between lymphadenopathy-associated virus seropositivity and transmission, nine couples (five heterosexual and four homosexual) at increased risk for acquired immune deficiency syndrome (AIDS) were studied. In two heterosexual couples, transmission of lymphadenopathy-associated virus from a seropositive man at increased risk to his monogamous wife occurred. In one couple, the wife of a man with hemophilia had lymphadenopathy-associated virus antibody and decreased T helper cells; in the other couple, the wife of a bisexual intravenous drug-user had AIDS. Neither woman had a recognized AIDS risk except marriage to a seropositive man at increased risk. However, study of the other couples revealed that regular sexual contact with seropositive persons over long periods did not always lead to evidence of lymphadenopathy-associated virus infection. This study suggests that presence of lymphadenopathy-associated virus antibody does not always indicate a high degree of infectivity.

We investigated whether serologic evidence of lymphadenopathy-associated virus (LAV), an exogenous human T-cell lymphotropic and cytopathic retrovirus, correlated with the acquisition and transmission of the acquired immunodeficiency syndrome (AIDS). Serum from 17 of 25 patients with AIDS contained circulating IgG anti-LAV antibody (all of 5 adults with cancer and 6 of 12 adults and 6 of 8 children with opportunistic infections, with or without Kaposi's sarcoma). All of eight homosexual men with generalized lymphadenopathy or the AIDS-related complex and five homosexual men with AIDS prodromes who subsequently had AIDS were also seropositive. The anti-LAV antibody was not found in 99 of 100 healthy blood donors or in 23 patients with genetic immunodeficiencies, supporting the contention that LAV is unlikely to represent simply another opportunistic microorganism. An AIDS carrier state was indicated by the probable transfer of LAV from asymptomatic, immunologically competent mothers to their offspring. These data offer a basis for the hypotheses that LAV is a marker for AIDS, may be carried and transmitted in the absence of clinical findings or in vitro T-cell abnormalities, and is probably an etiologically important agent in AIDS and its prodromes.

We present evidence of transmission of lymphadenopathy-associated virus (LAV)/human T-lymphotropic virus type III (HTLV-III) from a man to his wife, and a return to a normal number of T-helper lymphocytes and loss of antibody after discontinuing sexual exposure to LAV/HTLV-III. The man had hemophilia A, and developed the lymphadenopathy syndrome, antibody to LAV, and a low number of T-helper lymphocytes. His wife, who had no risks for the acquired immunodeficiency syndrome other than sexual contact with him, developed LAV antibody (titer, 1:160) and a mildly decreased number of T-helper cells. The husband subsequently developed the syndrome and lost the LAV antibody. During 10 months of follow-up his wife remained clinically well, discontinued exposure to semen, and then lost the LAV antibody, and regained a normal number of T-helper cells.

49 French haemophiliacs (haemophilia A: 41 patients; haemophilia B: 8 patients) were serologically testes for lymphadenopathy-AIDS virus antibodies: 10 patients (20.4%) were seropositive including 9 (21.9%) with haemophilia A and 1 (12.5%) with haemophilia B. Among haemophiliacs A, seropositive patients received significantly larger amounts of factor VIII concentrate during the 2 years preceding the study.

IgG antibodies to lymphadenopathy-associated virus ( LAV ) were found by a specific enzyme-linked immunosorbent assay in 18/48 (37.5%), patients with acquired immunodeficiency syndrome, 38/51 (74.5%) patients with lymphadenopathy syndrome, 8/44 (18%) homosexual men without lymphadenopathy, and 1/100 unselected blood donors.

Lymphadenopathy-associated virus ( LAV ), a human T- lymphotrophic retrovirus isolated from a homosexual man with lymphadenopathy, has been causally associated with acquired immunodeficiency syndrome (AIDS). A sensitive and specific radioimmunoprecipitation test was developed for the detection of antibodies to the major core protein of LAV , p25 (molecular weight 25,000). Antibody to LAV p25 was found in the serum of 51 of 125 AIDS patients, 81 of 113 patients with lymphadenopathy syndrome, 0 of 70 workers at the Centers for Disease Control (some of whom had handled specimens from AIDS patients), and 0 of 189 random blood donors. Of a group of 100 homosexual men from San Francisco whose serum was obtained in 1978, only one had antibody to LAV p25; in contrast, of a group of 50 homosexual men in the same community whose serum was obtained in 1984, 12 had antibodies to LAV p25.

Twenty-six sera containing anti-HIV antibodies from individuals with AIDS, AIDS-related complex, lymphadenopathy syndrome, or from seropositive individuals without clinical symptoms, were tested for the presence of natural autoantibodies (NAb) to actin, DNA, tubulin, thyroglobulin, albumin, myosin and TNP-BSA. Sera from 22 seronegative individuals at high risk for HIV infection were also examined. NAb titres to all these antigens were found to be elevated in both groups as compared to the titres in pooled normal human sera. The most prevalent NAb were those of the IgG class directed against TNP found in high titre in seropositive individuals. On the basis of the above results, sera from 50 anti-HIV-positive and 67 anti-HIV-negative individuals were tested for IgG antibody activity against a panel of protein antigens with different degrees of TNP substitution. The greater the TNP substitution, the higher the titres of IgG antibodies detected in anti-HIV-positive sera. Antibody titres in seronegative individuals at high risk for HIV infection were independent of the degree of TNP substitution. In almost all cases, the highest titres of IgG anti-TNP antibodies were found in anti-HIV-positive sera from individuals with clinical manifestations.

HIV-1 infected Molt4-T4 cells provide an efficient system for the production of cellular precursor gp160 of HIV envelope glycoproteins, gp120 and gp41. The precursor gp160 was purified on an immuno-affinity column containing antibodies from sera of HIV-1-seropositive patients. The precursor gp160 was then isolated by preparative polyacrylamide gel electrophoresis. Two out of four Balb/c mice, immunized with these purified preparations of gp160, developed specific circulating antibodies. A hybridoma cell line was subsequently isolated producing monoclonal antibody KL49/19 (IgG1, K) specific for gp160. This monoclonal antibody can specifically immunoprecipitate gp160, existing in HIV-1-infected cells. In an immunoblotting assay, it identifies mainly gp160 and shows a slight affinity for the mature glycoprotein, gp120. The monoclonal antibody is probably directed against an epitope in the polypeptide residue of gp160 since it can recognize a deglycosylated polypeptide of molecular weight 90,000, a product of gp160 digestion by endoglycosidase H (Endo H). It does not cross-react with any protein of HIV-2 by immunoblot or immunoprecipitation assays. By virtue of its specificity, the monoclonal antibody KL49/19 might provide a powerful probe with which to detect gp160 in cells which might partially express the HIV-1 genes.

The presence of antibodies to lymphadenopathy-associated retrovirus (LAV) was determined by a radioimmunoprecipitation assay and by an enzyme-linked immunosorbent solid assay of sera from Zairian patients with the acquired immune deficiency syndrome (AIDS) in 1983. Thirty-five of 37 patients (94 percent) and 32 of 36 patients (88 percent), respectively, were seropositive by the two tests. In a control group of 26 patients, six (23 percent) showed positive results in these tests. Of these six control patients, five had clinically demonstrable infectious diseases and a low ratio of T4 to T8 lymphocytes. In addition, sera collected from a control group of Zairian mothers in 1980 were positive for LAV in 5 of 100 cases. Other serologic data suggest that LAV was present as early as 1977 in Zaire.

A human retrovirus was isolated from the peripheral blood of three American patients newly diagnosed with the acquired immunodeficiency syndrome (AIDS). In each case the major core viral protein (p25) was shown to be antigenically identical to that of the prototype lymphadenopathy-associated virus (LAV). Two of the viral isolates were derived from intravenous narcotics abusers, the first demonstration of LAV isolation from this risk group. Antibody to LAV was detected by an IgG enzyme-linked immunosorbent assay in the serum samples of these and 14 additional American patients with AIDS and in none of 12 hospital worker controls. These findings provide support for the etiologic association of LAV and AIDS.