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Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 253 records · Page 14Linked to original sources
PubMed1988

Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism.

The effect of weak bases (NH4Cl and amantadine) and carboxylic ionophores (monensin) on the infection of CD4 (T4) positive human cell lines by HIV-1 is examined. These reagents, which raise the pH of acidic intracellular organelles, fail to inhibit HIV-1 entry and the events leading to viral protein synthesis at concentrations inhibitory for low pH-dependent fusogenic enveloped viruses. The infectivity of VSV (HIV-1) pseudotypes is unaffected by weak bases at concentrations causing 95% plaque reduction of VSV in its own envelope. HIV-1 dependent cell--cell fusion (syncytium formation) occurs in medium maintained at pH 7.4-7.6, and virions are not irreversibly inactivated by incubation in acid medium. Our results show that HIV-1 entry and membrane fusion do not require exposure to low pH. The production of infectious HIV-1 particles, however, is inhibited in cells treated with NH4Cl.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Lack of reverse transcriptase activity in serum in sporadic post-transfusional and presumed epidemic or water-borne forms of severe non-A, non-B hepatitis.

Reverse transcriptase (RT) activity was not detected in any serum sample taken from 22 patients with mainly severe non-A, non-B hepatitis (NANBH), using two assays selected to cover the range of known human and animal retroviruses. The study included patients with fulminant and sub-acute hepatic failure, which was was attributed to sporadic, post-transfusional, and presumed epidemic or water-borne epidemiological forms of NANBH. Although we cannot exclude the possibility that some of the agents implicated in NANBH are retroviruses, our negative findings suggest that other agents may be involved at least in the severe forms of NANBH.

Adolescent↗
PubMed1988

Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide.

Three IgM monoclonal antibodies raised against synthetic peptide analogs of a hydrophilic region of the gp41 transmembrane env protein of HIV-1 neutralize different HIV-1 isolates but not HIV-2 isolates, as determined by HIV titration and by syncytial inhibition assays. VSV (HIV-1) pseudotypes, however, were not neutralized, indicating that gp41 was not accessible to these antibodies on the pseudotype particles. The antibodies affect early steps in adsorption and penetration of HIV-1.

Antibodies, Monoclonal↗
PubMed1988

Possible genetic predisposition to idiopathic focal segmental glomerulosclerosis.

HLA-A, B, and DR antigen frequencies were studied in a group of 57 patients to determine possible inborn susceptibility to idiopathic focal segmental glomerulosclerosis (FSGS). There were 34 white patients and 23 black patients, most of whom had nephrotic syndrome and later developed renal failure. HLA-DR4 was significantly increased in both patient groups when compared with their respective control groups. This association has not been previously reported. Of note, the association with DR4 was most striking in patients with adult onset disease (in blacks, relative risk equals 5.2; in whites, relative risk equals 5.8). No other antigen was increased in both patient groups but HLA-A28 was increased in blacks. These data support the notion of genetic predisposition to focal segmental glomerulosclerosis in two different ethnic groups.

Adolescent↗
PubMed1988

Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120.

The major envelope glycoprotein, gp120, of human immunodeficiency virus type 1 (HIV-1) was purified from a Chinese hamster ovary cell line transfected with a truncated form of the HIV-1 env gene. The recombinant glycoprotein (rgp120) was formulated with aluminum hydroxide adjuvant and was used to immunize chimpanzees. The recombinant preparation was effective in eliciting cellular and humoral immunity as well as immunologic memory. Anti-rgp 120 antibodies reacted with authentic viral gp120 in immunological blot assays and were able to neutralize HIV-1 infectivity in vitro. Sera from the rgp120-immunized animals were able to neutralize HIV-1 pseudotypes of vesicular stomatitis virus prepared from the IIIB isolate, from which the gene encoding rgp120 was derived, as well as two heterologous isolates, ARV-2 and RF. The immune response elicited against the rgp120 was not effective in preventing viral infection after intravenous challenge with HIV-1. The implications of these results on HIV-1 vaccine development are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Modulation of rat bronchoalveolar lavage cell function by the intratracheal delivery of interferon-gamma.

To determine if there is a rationale for compartmentalized immunostimulation, we have carried out a series of experiments to evaluate whether intratracheal delivery of interferon-gamma (rRatIFN-gamma) can activate rat bronchoalveolar lavage cells (BAL) for in vitro expression of tumoricidal activity against xenogeneic P815 tumor cells and enhanced in vitro microbicidal activity against the intracellular protozoan Toxoplasma gondii. Treatment of rat alveolar macrophages in vitro activates them for both of these activities as well as enhanced production of superoxide anion. We found that a single intratracheal dose of 5,000-10,000 units of rRatIFN-gamma activated rat BAL for both microbicidal and tumoricidal activity. To determine the duration of activation, microbicidal activity was determined 1, 2, 3, 5, and 7 days after a single intratracheal dose of 5,000 units of IFN. Enhanced microbicidal activity was maintained through day 3 but returned to control levels by day 5. Alveolar macrophages always accounted for the majority of cells in the lavage populations. However, intratracheal IFN caused an increase in the number of polymorphonuclear leukocytes and lymphocytes in the lavageable cells and, although these cells were always in the minority, they may have contributed to both the tumoricidal and microbicidal activity of the lavage cells. These studies demonstrate that local administration of an immunostimulant can activate pulmonary defense cells and may be a feasible route of drug delivery for prophylaxis against pulmonary infections.

Animals↗
PubMed1988

Neutralizing monoclonal antibodies to the AIDS virus.

The production of neutralizing monoclonal antibodies (MAbs) will permit the exact localization of neutralizing epitopes on the AIDS virus, HIV-1. We describe the properties of seven MAbs to the envelope of the LAV-1 isolate. Five MAbs recognise the central portion of gp110, amino acids 279-472, and four of these are capable of high-titre neutralization of HIV-1, by infection inhibition, syncytial inhibition and vesicular stomatitis virus (VSV) pseudotype neutralization. One of the two MAbs to gp41 inhibits syncytium formation. Neutralization, live cell immunofluorescence and immunoprecipitation of gp110 are type-specific and restricted to HIV-1 isolates closely related to LAV-1.

Antibodies, Monoclonal↗
PubMed1988

HIV-2 antisera cross-neutralize HIV-1.

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.

Antibodies, Viral↗
PubMed1988

The human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV interact with similar epitopes on their cellular receptor, the CD4 molecule.

The cellular receptor for HIV-1 is the leucocyte differentiation antigen, CD4. Blocking of HIV-1 infectivity can be achieved with monoclonal antibodies (MAbs) to some, but not all epitopes of this antigen. We demonstrate here, by inhibition of virus infection, blocking of syncytium formation and inhibition of pseudotype infection with a panel of CD4 MAbs, that HIV-1, HIV-2 and simian immunodeficiency virus (SIV) isolates share the same cellular receptor, the CD4 glycoprotein. It is also shown that very similar epitopes of this molecule are involved in virus binding. We infer from these data that the binding sites on these viruses are highly conserved regions, and may therefore make good targets for potential vaccines. In addition, we show that cell surface expression of CD4 is similarly modulated after infection of cell lines by all the viruses.

Animals↗
PubMed1988

Human immunodeficiency viruses: neutralization and receptors.

The envelope glycoproteins of HIV, gp120 and gp41, contain epitopes recognized by neutralizing antibodies. Studies of human sera from infected individuals indicate that group-specific neutralization antigens common to most isolates of HIV-1 exist, and that some HIV-2 antisera cross-neutralize HIV-1. Neutralization epitopes for HIV-1 have been identified and mapped, including a group-specific antigen on gp41, and a type-specific antigen on gp120. Neutralization "escape" mutants have been selected in vitro with a neutralizing mab to the type-specific antigenic loop. The CD4 antigen binds HIV-1 gp120 with high affinity and acts as the receptor on human and simian T-lymphocytes and monocytes for all strains of HIV-1, HIV-2, and SIV tested. Following binding to the CD4 receptor, HIV becomes internalized by a pH-independent process. The principle binding domain for gp120 is located in the N-terminal V domain of CD4. Anti-idiotypic sera to CD4 mabs recognizing the same site weakly neutralize HIVs of many strains, and soluble, recombinant forms of CD4 strongly neutralize HIV. Neither anti-CD4 mabs nor sCD4 inhibit the low level of plating of HIV observed on tumour cells in culture of glial (brain) and muscle origin, indicating that CD4 is not essential for infection of these cell types.

Animals↗
PubMed1988

Virology. Overview.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis.

Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.

AIDS-Related Complex↗