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Biomedical subjects

D Guetard

Publications and source records attributed to D Guetard.

30 records · Page 2Linked to original sources

HIV-2 in rhesus monkeys: serological, virological and clinical results.

Diseases induced by animal retroviruses are not considered to be good models for the human acquired immunodeficiency syndrome (AIDS) at present. The lack of an animal model for the human immunodeficiency virus (HIV) infection presents a main problem in the complete understanding of the pathogenesis of HIV-mediated diseases. Because of the homologies between simian immunodeficiency virus (SIV) and HIV-2, we inoculated rhesus monkeys with HIV-2 and HIV-2 adapted in vitro to monkey cells. One of the ten animals inoculated developed clinical symptoms that might be related to the infection with HIV-2.

Acquired Immunodeficiency Syndrome↗

Induction of anti-human immunodeficiency virus (HIV) neutralizing antibodies in rabbits immunized with recombinant HIV--hepatitis B surface antigen particles.

Fragments of the human immunodeficiency virus (HIV) envelope coding region have been fused with the hepatitis B virus envelope middle protein. In this system, HIV antigenic determinants are exposed at the surface of a highly antigenic structure, the hepatitis B surface antigen particle. Immunization of rabbits with these particles elicited antibodies directed against both parts of the hybrid protein. One of the rabbit antisera not only exhibited a neutralizing effect on the original HIV1 isolate but also on a divergent Zairian isolate. The HIV sequence in this recombinant is 84 amino acids long and contains conserved and variable domains and a region critical for interaction with the CD4 receptor. Such recombinant antigens could be primary elements in the design of a polyvalent vaccine.

Animals↗

Human immunodeficiency virus type 2 infection associated with AIDS in West Africa.

We recently reported the isolation of a new retrovirus, termed human immunodeficiency virus type 2 (HIV-2), from two West African patients with the acquired immunodeficiency syndrome (AIDS). This virus is related to but distinct from the well-characterized AIDS retrovirus, human immunodeficiency virus type 1 (HIV-1). We report here evidence of infection with HIV-2 in 30 patients, almost all from West Africa. Seventeen of them had a clinical syndrome indistinguishable from AIDS (7 of these 17 died). Others had either the AIDS-related complex or no HIV-related symptoms. All patients had serum antibodies reacting with HIV-2 in an indirect immunofluorescence assay. All serum tested contained antibodies reacting with the envelope glycoprotein of the virus in an immunoprecipitation assay. Cross-reactivity of serum antibodies with HIV-1 was detected in a minority of patients and varied according to the assay used. Retroviral isolates were obtained from the blood lymphocytes of 11 patients and were all identified as HIV-2 by nucleic acid hybridization; none hybridized with an HIV-1 probe. These findings indicate that some cases of AIDS in West Africa may be caused by HIV-2, but the extent of the spread of this virus and its clinical correlates will require careful epidemiologic investigation.

AIDS-Related Complex↗

Induction of EBV DNA demethylation and of EBV-specific transcription in Daudi cells treated with TPA and n-butyrate.

The Epstein-Barr virus (EBV) abortive producer cell line Daudi may be induced to an incomplete cycle of viral production by chemicals such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-butyrate. These chemicals greatly increase expression of the early antigen but not that of viral capsid antigen. DNA from these cells was cleaved with various restriction enzymes specific for the mCG sites. Viral sequences (mostly in an episomal form) were tested for their methylation patterns and compared to the methylation pattern of the producer cell line B95-8. The BamHI C, V, and H EBV DNA fragments appeared to be nonmethylated in B95-8 whether or not induced by TPA. The same fragments were partially methylated in noninduced Daudi cells. Treatment of the latter with TPA and n-butyrate increased the amount of viral DNA per cell, and hypomethylation of some EBV DNA sites occurred in parallel. Transcription changes were noted only at the level of the BamHI H fragment; cytoplasmic RNA molecules specific for this region were detected only after induction.

Burkitt Lymphoma↗

The effect on macromolecular synthesis of amino acid deprivation of hamster kidney cells.

Since asparagine has been found to inhibit growth of some tumors and to inhibit or delay mitotic activity in other cells, we have studied the effect of asparaginase and of deprivation of some essential amino acids (Arg, Asn, Leu, Ile, Trp) on nucleic acid and protein synthesis in an asparagine-requiring strain of BHK/21 cells. We find that: (1) there is no essential difference in the pattern of synthesis following deprivation of any of the amino acids we tested; (2) that the effect of asparaginase is similar to that of amino acid deprivation; (3) that RNA synthesis is inhibited more rapidly than DNA or protein synthesis; (4) that after 10 hr of amino acid starvation, DNA synthesis is almost totally (reversibly) inhibited while RAN synthesis continues at about 30-50% and protein at about 100% of the initial value.

Amino Acids↗

Spermatozoa as potential carriers of HIV.

In order to investigate the role of germ cells in the sexual transmission of immunodeficiency virus (HIV), spermatozoa from healthy HIV-seronegative men were incubated in vitro with HIV1. After washing, they were cocultured with peripheral blood leukocytes from seronegative blood donors. Reverse transcriptase assays and p24 antigen tests were performed in culture supernatants. Electron microscopy examination of these HIV-incubated spermatozoa was carried out, as well as the search for CD4 molecules on their surface. Although virus bound to and seemed to enter spermatozoa despite the absence of detectable CD4 epitopes on their surface, no replication of HIV was apparent. However, HIV particles on the surface of spermatozoa were capable of infecting CD4 T lymphocytes. Present results would seem to preclude artificial insemination between an HIV-seropositive man and an HIV-seronegative woman.

Adult↗

T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV.

Many viruses, including retroviruses, are characterized by their specific cell tropism. Lymphadenopathy-associated virus (LAV) is a human lymphotropic retrovirus isolated from patients with acquired immune deficiency syndrome (AIDS) or related syndromes, that displays selective tropism for a subset of T lymphocytes defined by the expression of a surface glycoprotein of relative molecular mass 62,000 (62K) termed T4 (refs 6-8). This glycoprotein delineates a subset of T lymphocytes with mainly helper/inducer functions, while T lymphocytes of the reciprocal subset express a glycoprotein termed T8, have mainly cytotoxic/suppressor activities, and are unable to replicate LAV. Such a tropism may be controlled at the genomic level by regulatory sequences, as described for the human T-cell leukaemia viruses HTLV-I and -II (refs 2, 3). Alternatively or concomitantly, productive cell infection may be controlled at the membrane level, requiring the interaction of a specific cellular receptor with the virus envelope, as demonstrated recently for Epstein-Barr virus (EBV). Therefore, we have investigated whether the T4 molecule itself is related to the receptor for LAV. We report here that preincubation of T4+ lymphocytes with three individual monoclonal antibodies directed at the T4 glycoprotein blocked cell infection by LAV. This blocking effect was specific, as other monoclonal antibodies--such as antibody to histocompatibility locus antigen (HLA) class II or anti-T-cell natural killer (TNK) target--directed at other surface structures strongly expressed on activated cultured T4+ cells, did not prevent LAV infection. Direct virus neutralization by monoclonal antibodies was also ruled out. These results strongly support the view that a surface molecule directly involved in cellular functions acts as, or is related to, the receptor for a human retrovirus.

Antibodies, Monoclonal↗