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Biomedical subjects

M Robert-Guroff

Publications and source records attributed to M Robert-Guroff.

131 records · Page 8Linked to original sources

Induction of endogenous murine C-type virus in spleen cell cultures treated with mitogens and 5-bromo-2'-deoxyuridine.

In short-term cultures of BALB/c spleen cells, treatment with a combination of 5-bromo-2'-deoxyuridine (BrdU) and either lipopolysaccharide W. Escherichia coli or concanavalin A resulted in release of C-type virus into the medium. Only lipopolysaccharide induced virus release when given alone. This could be potentiated by a combined treatment with BrdU. In contrast, phytohemagglutinin at mitogenic concentration had no effect with or without BrdU, suggesting that inducibility may vary between various mitogen-responsive spleen cell populations. In AKR mice, spontaneous virus release was detectable in nonstimulated spleen cell cultures. This could be potentiated by lipopolysaccharide, whereas no further increase occurred upon additional BrdU treatment. The induced viruses had C-type characteristics in that they contained reverse transcriptase that could be distinguished from cellular enzymes by template-primer preference experiments. Furthermore, the enzyme activities were particle-associated, banding in isopycnic sucrose gradients at 1.15-1.17 g/cm-3. The presence of C-type viruses was confirmed by electron microscopy.

Animals↗

HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex.

The isolation of the human T-cell leukaemia (lymphotropic) virus type III (HTLV-III or lymphadenopathy-associated virus) from cells of many patients with acquired immune deficiency syndrome (AIDS) presented the first evidence that the virus was the aetiological agent of the disease. Subsequent seroepidemiological studies have shown the presence of HTLV-III-specific antibodies in the serum of most patients with AIDS and AIDS-related complex (ARC), and in the serum of many individuals at risk for AIDS. Despite these extensive studies, there are no reports of protective effects of HTLV-III antibodies. In contrast, neutralizing antibodies specific for HTLV-I and -II have been identified previously. Therefore, we investigated whether HTLV-III-exposed individuals possess antibody activities capable of inhibiting viral infection. Here, we report that natural antibodies capable of neutralizing HTLV-III infection of H9 cells were detected in most adults AIDS and ARC patients but in no normal healthy heterosexual controls. Geometric mean antibody titres in ARC patients were double those in AIDS patients, and were even higher in two antibody-positive healthy homosexuals. This suggests that virus neutralizing antibodies may exert an in vivo protective effect. The presence of these antibodies indicates an immunological response to HTLV-III which potentially may be manipulated for therapeutic advantage. The methodology used here will be useful in monitoring future vaccine approaches.

Acquired Immunodeficiency Syndrome↗

Multiple sclerosis and human T-cell lymphotropic retroviruses.

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Adolescent↗

Expression of the HTLV-III envelope gene by a recombinant vaccinia virus.

The discovery that the aetiological agent of acquired immune deficiency syndrome (AIDS) is a retrovirus, referred to as human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV) (for review see ref. 1), has raised the possibility of developing a vaccine. In this regard, the envelope (env) proteins of murine retroviruses can induce protective immunity in mice. The HTLV-III env gene specifies a primary polypeptide of approximately 860 amino acids that is glycosylated to form a precursor of relative molecular mass (Mr) 160,000 (gp160), which gives rise to mature membrane-associated proteins of Mr 120,000 (gp120) and 41,000 (gp41). The HTLV-III env gene has been expressed in Escherichia coli and by simian virus 40 (SV40) vectors but formation of the authentic proteins has not been demonstrated. Here, we describe the expression of the complete env gene by a vaccinia virus vector. Evidence is presented that synthesis, glycosylation, processing and membrane transport of the env polypeptide occurred without other HTLV-III gene functions; the env protein was recognized by sera from unrelated AIDs patients; and a single vaccination with the infectious recombinant vaccinia virus induced antibodies to gp120 in mice.

DNA, Recombinant↗