Biomedical subjects

J Goudsmit

Publications and source records attributed to J Goudsmit.

401 records · Page 23Linked to original sources

PubMedDate not supplied

Antibody recognition of amino acid divergence within an HIV-1 neutralization epitope.

Antibodies elicited by HIV-1 strains, and which neutralize such strains in vitro, bind to synthetic peptides of 5-8 amino acids in length. These amino acids, although variable, have a fixed location between two cysteines in the carboxyl terminus of the HIV-1 external envelope. Nine peptides of 9 amino acids corresponding to the gp120 domains of European and American (LAV-1, NY5, CDC4, SF2), Haitian (RF) and African (ELI, MAL, Z3, Z6) HIV-1 strains, were synthesized using LAV-1 and RF neutralization epitopes as models. Serum of chimpanzees infected with LAV-1, HTLV-IIIB or HTLV-IIIRF reacted predominantly with the homologous peptide, although cross-reactivity with heterologous peptides occurred: 8 out of 11 human sera with HTLV-IIIB-neutralizing activity bound the LAV-1/HTLV-IIIB peptide, and 6 out of 7 sera with HTLV-IIIRF-neutralizing activity bound the RF peptide. African sera reacted most frequently with the Z3 peptide (78%) while only 35% (p = 0.0001) of European and 20% (p less than 0.0001) of American sera recognized it. Recognition patterns of children from the USA and Europe were different. Although multiple reactivities were observed, blocking experiments favoured cross-reactivity as the explanation. Based on the antibody profiles of nonapeptide recognition, peptides LAV-1, RF and SF2 were clustered, as were NY5 and CDC4, and so were Z6, MAL and ELI. This antigenic relatedness of HIV-1 strains could not entirely be explained by the physico-chemical characteristics of the nonamers per se. Resemblance was observed with the clustering of HIV-1 strains based on the divergence of the nucleotide sequence of entire HIV-1 envelopes. This implies a role of peripheral envelope residues, in the context of infectious particles or infected cells, in determining the specificity of antibodies reactive to the V3 domain. Therefore, the neutralization domain in this variable region may be considered part of a conformational structure involving several envelope regions which appear distinct from each other in the primary sequence.

Amino Acids↗

PubMedDate not supplied

IgG antibodies to HTLV-III associated antigens in patients with AIDS and at risk for AIDS in The Netherlands.

Thirty-nine homosexual males, 11 of whom suffered from AIDS and 13 from Lymphadenopathy Syndrome (LAS), 18 healthy hemophiliacs and 12 healthy blood donors, not belonging to any AIDS risk group, were tested for IgG antibodies to Human T-lymphotropic retrovirus type III (HTLV-III) by indirect immunofluorescence. All tested people were from the area of Amsterdam or from elsewhere in The Netherlands. Five of 11 AIDS patients, 8 of 13 LAS patients and 5 of 15 healthy homosexuals had antibodies to HTLV-III. Five of 18 healthy hemophiliacs were seropositive for HTLV-III. None of the 12 blood donors was seropositive for HTLV-III.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Induction in chimpanzees of antibodies inhibiting receptor-mediated cell fusion by HIV glycoprotein.

Cell fusion of HTLV-IIIB-infected EBV-transformed B cells and CD4+ T cells was inhibited by sera from eight of nine HIV infected chimpanzees. Syncytia formation was reduced by sixty percent relative to control after only 5 minutes of preincubation of the HIV infected cells with immune primate serum, indicating that these antibodies have high affinity for HIV protein on the surface of infected cells. Serum dilutions that blocked formation of syncytia irreversibly within 24 hrs also blocked expression of HIV antigens by the target CD4+ cells. Three of four animals inoculated with the LAV or HTLV-IIIB strain of HIV developed antibodies inhibiting CD4-dependent cell fusion by HIV glycoprotein (CFI-antibodies) 2-3 months after inoculation coincident with development of HIV specific IgG antibodies. Similar early CFI-antibody responses occurred in two second passage chimpanzees. In contrast, a chimpanzee infected with a third passage of LAV had a delayed CFI-antibody response, indicating that variants of HIV with divergent CFI epitopes did eventually emerge. Delayed development of CFI-antibodies (6-11 months after inoculation) relative to HIV specific IgG ELISA antibody was also seen in a chimpanzee on primary passage and a chimpanzee on second passage of HTLV-IIIB. No CFI-antibodies were detected in a chimpanzee following inoculation with human brain tissue, while antibodies to other structural proteins were recognized by immunoblotting. These results indicate that changes in CFI epitopes occur under immune pressure and that the appearance of CFI-antibodies depends on the time after infection and on the degree to which CFI epitopes of the inoculum strain diverge from those of the test strain.

Animals↗

PubMedDate not supplied

[Role of stabilizing and splitting selection in evolution of of viruses from the Parvoviridae and Astroviridae families].

We had previously collected and analyzed, by phylogenetic methods, all genetic data available now for the Parvoviridae and Astroviridae families, which made it possible to define the evolutionary relations between the viruses as well as to depict a variety of events in the evolutionary history of the two families. The offered case study is dedicated to investigating the stabilizing and splitting selection types in the evolution of the discussed viral families. We analyzed the number of synonymous and non-synonymous nucleotide substitutions in the coding genomes' regions of the viruses. Finally, the stabilizing selection was shown to be a key factor in the evolution of parvoviruses and astroviruses.

Animals↗

PubMedDate not supplied

[The molecular epidemiology of HIV-1 in Belarus in (1996-2004): a predominance of subtype A variants and circulation of subtype B variants].

To study the molecular epidemiology of HIV-1 in Belarus, the genetic sequences of HIV-1 variants were obtained from 50 infected persons, which represented the main stages, risk groups, and geographic areas of the epidemic. The env and gag sequences were studied for HIV-1 variants from 31 persons, the env sequences were for HIV-1 variants from 18 persons, and the gag sequence was for HIV-1 variant from 1 person. Phylogenetic analysis indicated that the sequences of HIV-1 variants from 46 persons were homogenic and evolutionally closely related to IDU-A strains specific for other epidemics in the former Soviet Union are dominating in the epidemic in Belarus. Circulation of epidemiologically unrelated subtype B viruses was also established.

Female↗