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Lymphadenopathy-associated virus (LAV) is a human retrovirus first isolated from a homosexual patient with lymphadenopathy syndrome, frequently a prodrome or a benign form of acquired immune deficiency syndrome (AIDS). Other LAV isolates have subsequently been recovered from patients with AIDS or pre-AIDS and all available data are consistent with the virus being the causative agent of AIDS. The virus is propagated on activated T lymphocytes and has a tropism for the T-cell subset OKT4 (ref. 6), in which it induces a cytopathic effect. The major core protein of LAV is antigenically unrelated to other known retroviral antigens. LAV-like viruses have more recently been independently isolated from patients with AIDS and pre-AIDS. These viruses, called human T-cell leukaemia/lymphoma virus type III (HTLV-III) and AIDS-associated retrovirus (ARV), seem to have many characteristics in common with LAV and probably represent independent isolates of the LAV prototype. We have sought to characterize LAV by the molecular cloning of its genome. A cloned LAV complementary DNA was used to screen a library of recombinant phages constructed from the genomic DNA of LAV-infected T lymphocytes. Two families of clones were characterized which differ in a restriction site. The viral genome is longer than any other human retroviral genome (9.1-9.2 kilobases).

A strain of lymphadenopathy associated retrovirus ( LAV ) passaged in vitro was used to infect a lymphoblastoid cell line obtained by transformation with Epstein-Barr virus of B lymphocytes from a healthy donor. The virus produced from this line (B- LAV ) was also able to grow at a high rate in some other lymphoblastoid lines and in a Burkitt lymphoma line. This adapted strain retained the biochemical, ultrastructural, and antigenic characteristics of the original strain, as well as its tropism for normal T4+ lymphocytes. It is thus possible to grow LAV in large quantities that can be used for the preparation of diagnostic reagents. The interaction between such a human retrovirus and Epstein-Barr virus, a DNA virus, may have some implication for the pathology of the acquired immunodeficiency syndrome and related diseases.

In order to investigate the role of endogenous interferon in retrovirus production by infected or induced cells, the effect of two sera raised against mouse interferon has been tested on various C-type murine viruses. Addition of a highly potent anti-interferon serum to 3T3/IC cells chronically infected by the Moloney strain of MLV results in a considerable increase of virus production, as tested by reverse transcriptase assay. This effect is neutralized by an excess of exogenous interferon. The greatest effect of anti-interferon sera was obtained in the derepression of endogenous retroviruses: in K. BALB/c cells treated by IUDR, anti-interferon serum increases up to 50-fold the expression of the endogenous virus. The extinction of virus production which secondarily occurs after its induction by IUdR is likely to be caused by cellular endogenous interferon. The biological parameters of the viral agent produced in the presence of anti-interferon serum are those of the xenotropic endogenous virus.

Treatment of K/Balb cells with IdUrd leads to the expression of endogenous virus and interferon is formed which subsequently can suppress the release of virus into the medium. Under these conditions, a protein kinase activity capable of phosphorylating an endogenous polypeptide of apparent mol. wt. 67000 is detected. This kinase activity is analogous to that induced in K/Balb cells treated with exogenous interferon. The induction of the protein kinase activity in IdUrd-treated K/Balb cells can be blocked by anti-interferon serum, thus providing evidence for the presence and action of interferon.

Lymphadenopathy associated virus ( LAV ) has been isolated from patients with the acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome. Since the immune deficiency in AIDS seems to be primarily related to the defect of the helper-inducer T lymphocyte subset, the possibility that LAV is selectively tropic for this subset was investigated. Fractionation of T lymphocytes was achieved by cellular affinity chromatography with monoclonal antibodies. In a hemophilic patient who was a healthy carrier of LAV , reverse transcriptase activity and virus particles detected by electron microscopy were found only in cultures of helper-inducer lymphocytes. When infected with LAV in vitro, lymphocyte subsets from normal individuals yielded similar results. Virus production was associated with impaired proliferation, modulation of T3-T4 cell markers, and the appearance of cytopathic effects. The results provide evidence for the involvement of LAV in AIDS.

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.

Lymphadenopathy associated virus is inactivated by heating at 56 degrees C for 30 min, and is not inactivated by 2 X 10(5) rad gamma irradiation or 5 X 10(3) J/m2 ultraviolet irradiation.

Lymphadenopathy associated virus (LAV) is a novel human retrovirus first reported in 1983. It was isolated from the lymph node lymphocytes of a French homosexual patient with generalized hyperplasic lymphadenopathy. Subsequently LAV was isolated from patients with frank acquired immune deficiency syndrome (AIDS) coming from all the different high-risk groups, while anti-LAV antibodies were detected equally in individuals from all "at-risk" groups. Such a profile is consistent with the virus being the major etiological agent of AIDS. Furthermore its biological properties, namely its cytopathic effect in vitro, its T4-cell tropism as well as the role of the T4 molecule in virus infection explain, at least in part, the pathophysiology of AIDS. The major core (gag) proteins are p18, p25, and p13 which are products of a Pr55 precursor. The major envelope (env) glycoprotein is unusually large (gp110) for a retrovirus and comparable to those of the lentiviruses. Recently the virus has been molecularly cloned. The genome is 9.2 kb long, longer than any other known replication competent retrovirus apart from the lentiviruses. The absence of molecular hybridization between cloned LAV and human T-cell leukemia/lymphoma virus (HTLV) genomes compounds the original and extensive differences noted between these viruses and demonstrates that LAV is a prototype of a new class of human retrovirus.

A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.

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.