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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.

To define further the genetic variability of the human AIDS retrovirus, we have cloned and sequenced the complete genomes of two isolates obtained from Zairian patients. Their genetic organization is identical with that of isolates from Europe and North America, confirming a common evolutionary origin. However, the comparison of homologous proteins from these different isolates reveals a much greater extent of genetic polymorphism than previously observed. It is nevertheless possible to define conserved domains in the viral proteins, especially in the envelope, that could be of interest for the understanding of the molecular mechanisms of viral pathogenicity and for the development of diagnostic and therapeutic reagents.

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.

This article presents data obtained by our group in the molecular characterization of the probable agent of the acquired immune deficiency syndrome (AIDS), the lymphadenopathy/AIDS virus (LAV). Molecular cloning and complete nucleotide sequencing of LAV allows a detailed comparison with other AIDS virus isolates, as well as other human and animal retroviruses. We have now molecular evidence that the AIDS virus is closely related to visna virus, prototype of the lentiviruses, whereas the other human retroviruses, i.e., human T-cell leukemia viruses type I and II (HTLV-I and II), are quite remote in the evolution.

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.

We described here the characteristics of the Reverse Transcriptase activity associated with the Lymphadenopathy Associated Virus ( LAV ). A critical concentration of non ionic detergent, all four deoxyribonucleosides triphosphates and the divalent cation Mg2+ are required for optimal endogenous enzyme activity. The endogenous reaction product is digested by DNase and not by RNase and its synthesis is only slightly inhibited by actinomycin D. Exogenous reactions are optimal using poly A oligo dT12 -18 or poly Cm oligo dG12 -18 as template primer and Mg2+ as divalent cation. This enzyme can be distinguished from other cellular DNA polymerases activities and from Terminal deoxynucleotidyl Transferase (TdT) by purification from LAV infected T lymphocytes using phosphocellulose column.

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.

We recently reported the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of the AIDS epidemic now spreading in Central and East Africa, as well as the USA and Europe (see ref. 3 for review) both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. But preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1-positive sera. We now report the molecular cloning of the complete 9.5-kilobase (kb) genome of HIV-2, the observation of restriction site polymorphism between different isolates, and a preliminary analysis of the relationship of HIV-2 with other human and simian retroviruses.

The major envelope glycoprotein of the causative agent of Acquired Immune Deficiency Syndrome (AIDS) lymphadenopathy-associated virus (LAV) has been identified and characterized. The glycoprotein has an apparent molecular weight of 110,000-120,000 under denaturing conditions in polyacrylamide gel electrophoresis. Upon deglycosylation by a specific endoglycosydase, its size is reduced to 80,000. Cellular precursors of this glycoprotein have been detected with apparent molecular weight of 150,000 and 135,000. Nearly all AIDS and pre-AIDS patients have detectable antibodies against this viral glycoprotein.

Analysis of the nucleotide sequence of the human retrovirus associated with AIDS in West Africa, HIV-2, shows that it is evolutionarily distant from the previously characterized HIV-1. We suggest that these viruses existed long before the current AIDS epidemics. Their biological properties are conserved in spite of limited sequence homology; this may help the determination of the structure-function relationships of the different viral elements.

Reverse transcriptase activity of lymphadenopathy associated virus was assayed after exposure to various standard chemical disinfectants. 25% ethanol or 1% glutaraldehyde should prove sufficient to disinfect medical instruments, and 0.2% sodium hypochlorite for cleaning floors and benches. 0.1% formalin is too slow to be recommended.

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.

A murine monoclonal antibody (MAb), named C.V.K., was produced after immunization with highly purified and sonicated lymphadenopathy-associated virus (LAV). No monoclonal antibody was observed with intact virus used as immunogen. C.V.K. MAb recognizes an epitope present on the precursor gag protein of 55 kilodaltons. Western blot analysis and pulse-chase experiments support the interpretation that after p55 cleavage into p25, p18, and p13, only p18 expresses this epitope. C.V.K. MAb selectively stained only LAV-infected lymphocytes. This intracytoplasmic staining appears 3 days after the infection and is correlated with reverse transcriptase activity. Neither membrane immunofluorescence of infected lymphocytes nor neutralizing activity was observed with C.V.K. MAb. These facts suggest that p55 and p18 are not expressed at the cell membrane or on the viral envelope. C.V.K. MAb should prove useful not only in the purification of core proteins but also for detecting infected cells producing the virus in suspension or on histologic sections.

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.

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.

Recent data indicate that the lymphadenopathy-associated virus (LAV) is morphologically similar to animal lentiviruses, such as equine infectious anemia and visna viruses. This finding, together with the cross-reactivity of the core proteins of LAV with those of the equine infectious anemia virus and a similarity in genome structure and biological properties, allows LAV to be placed in the retroviral subfamily of Lentivirinae. Molecular data indicate a high degree of genetic variation of the virus, especially in the envelope gene, which have important implications for the origin of the virus (the T4 lymphotropism may be a recently acquired property) and for future immunization. Another problem is the role of viral infection in the induction of irreversible immunodeficiency. This syndrome occurs in a minority of infected persons, who generally have in common a past of antigenic stimulation and of immune depression before LAV infection.