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Biomedical subjects

A de Ronde

Publications and source records attributed to A de Ronde.

47 records · Page 3Linked to original sources

Speed of progression to AIDS and degree of antibody response to accessory gene products of HIV-1.

Antibodies to E. coli-produced HIV-1 nef, rev, tat, vpu, and vpr proteins were measured by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 190 initially symptom-free men who were seropositive for these antibodies at entry into the study. In the men seroconverting for antibodies to structural proteins the levels of nef-, rev-, and tat-specific antibodies, but not of vpu-, and vpr-specific antibodies, within 3 months of seroconversion, appeared to be lower in the five men progressing to AIDS, compared with the men remaining symptom-free during follow-up. Analysis of the prevalence of previously described antibody profiles to these accessory gene products was carried out. In all HIV-1 antibody seroconverters and in those HIV-1 antibody seropositive men with 15 or more months of follow-up who progressed to AIDS, there was a shift from predominantly nef- and vpu-specific antibody negative profiles in the men developing AIDS in the early years of the study to predominantly nef- and vpu-specific antibody positive profiles in men who developed AIDS later. Rev- and tat-specific antibody negative profiles were dominant in men progressing to AIDS throughout follow-up. No vpr-specific antibody profile occurred preferentially in the men progressing to AIDS throughout follow-up. Low antibody reactivity to accessory gene products nef, rev, and tat appears, like low anti-core antibody reactivity, to be associated with progression to AIDS relatively rapidly after infection with HIV-1.

Acquired Immunodeficiency Syndrome↗

Antibody response to viral proteins U (vpu) and R (vpr) in HIV-1-infected individuals.

Antibodies to E. coli-produced HIV-1 vpr and vpu were determined by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 196 initially symptom-free men who were positive for such antibodies at study entry. First detection of vpr- and vpu-specific antibodies always was within 12 months of seroconversion for antibodies to structural proteins. In the combined cohort of 268 men, vpr- and vpu-specific antibodies were found persistently in 26 and 43% of men, respectively. Vpr- and vpu-specific antibodies were transiently detected in 3 and 7%, respectively, and intermittently detected in 18 and 13% of men, respectively. No association was found between the patterns of vpr- or vpu-specific antibody response and clinical outcome. In subjects with different patterns of vpr- and vpu-specific antibody response, no clear temporal relationship existed between the appearance or disappearance of antibodies and the onset of HIV-1-related disease.

Cross-Sectional Studies↗

The SV40 small t antigen is essential for the morphological transformation of human fibroblasts.

The morphological transformation of human fibroblasts as measured in an assay for dense focus formation required, besides the SV40 large T antigen, an intact SV40 small t antigen. Using a G418-resistant colony formation assay it also was found that expression of the SV40 large T antigen only is not sufficient for the morphological transformation of human fibroblasts. Therefore it is concluded that the SV40 small t antigen is essential for the morphological transformation of human fibroblasts.

Animals↗

Antibody response to the viral negative factor (nef) in HIV-1 infection: a correlate of levels of HIV-1 expression.

Antibody responses against the nef gene product of HIV-1 were determined in sequential sera from a longitudinally studied cohort of 194 initially asymptomatic HIV-1-seropositive individuals and 72 individuals who seroconverted for antibodies to HIV-1 structural proteins (gag/env). In the majority of men, nef-specific antibodies, once detected, persisted (67.6%). In some men, nef-specific antibodies were only transiently (6.8%), or intermittently (5.3%), detectable. No nef-specific antibodies were found in the remaining men (20.3%). Nef-specific antibodies were elicited early in infection, but rarely (2/72 men) prior to seroconversion for antibodies to HIV-1 structural proteins. An absent, transient, or intermittent nef-specific antibody response was significantly associated with the absence or disappearance of antibodies to HIV-1 core proteins, with (re)appearance and persistence of HIV-1 core antigen and with the presence of low CD4+ cell numbers, i.e. profiles previously shown to be predictive of rapid disease progression. Although more cases of AIDS and AIDS-related disease (21/86 versus 28/180) occurred in the nef-specific antibody-negative group than in the nef-specific antibody-positive group, this difference did not reach significance.

Acquired Immunodeficiency Syndrome↗

Morphological transformation by early region human polyomavirus BK DNA of human fibroblasts with deletions in the short arm of one chromosome 11.

Human fibroblasts derived from four individuals with various deletions in the short arm of one chromosome 11 were susceptible to morphological transformation by early region BK virus DNA, whereas diploid human fibroblasts were not. This difference in susceptibility to transformation by early region BK virus DNA might be explained by a putative 'transformation suppressor' locus situated within the deleted region on the short arm of chromosome 11.

BK Virus↗

The early enhancer-promoter of BKV and host range for transformation.

The early genes of the human papovavirus BKV and simian virus 40 (SV40) show a different host range for transformation. The early region of SV40 efficiently transforms human fibroblast cells, whereas the early region of BKV does not. Interchanging noncoding enhancer-promoter sequences around the origin of replication between BKV and SV40 showed that the early enhancer-promoter sequences of BKV and SV40 could substitute for each other, as far as the induction of expression of tumor antigens and morphological transformation is concerned; the efficiency of transformation was influenced by the enhancer-promoter sequences, and the difference in host range for transformation between BKV and SV40 was determined by the early gene products rather than by the enhancer-promoter sequences.

Animals↗

Two domains within the early coding region of SV40 involved in the transformation of human fibroblasts.

The early gene products of simian virus 40 (SV40) transform human fibroblasts, whereas those of the human papovavirus BK (BKV) do not. The early gene products of both SV40 and BKV transform baby rat kidney cells. SV40-BKV chimerics were constructed which were able to transform baby rat kidney cells. Using the SV40-BKV chimerics, two domains within the SV40 large T protein were identified which are involved in the transformation of human fibroblasts.

Animals↗

Feline immunodeficiency virus subunit vaccines that induce virus neutralising antibodies but no protection against challenge infection.

Three experimental vaccines against feline immunodeficiency virus (FIV), all based on viral antigens presented via immune stimulating complexes (iscoms), were tested for their capacity to induce protection in cats from FIV infection. The respective vaccines consisted of FIV propagated in Crandell feline kidney (CrFK) cells (FIV-iscoms); FIV-iscoms spiked with recombinant vaccinia virus expressed FIV envelope glycoprotein incorporated into iscoms (FIV-iscoms + vGR657x15-iscoms) and vGR657x15-iscoms spiked with recombinant FIV Gag protein incorporated into iscoms (vGR657x15-iscoms + FIV-Gag-iscoms). Simian immunodeficiency virus envelope glycoprotein incorporated into iscoms, iscoms prepared with uninfected CrFK cells, and PBS served as controls. All cats vaccinated with vGR657x15-iscoms combined with FIV-iscoms or FIV-Gag-iscoms developed Env-specific plasma antibody responses. These antibodies neutralised FIV infection in CrFK cells, but failed to neutralise FIV infection in primary feline thymocytes. FIV-iscoms induced poor Env-specific responses and only one out of six cats developed antibodies that neutralised FIV in the CrFK cell based assay. Four weeks after challenge all cats proved to be infected, showing that none of the vaccine preparations provided protection. In contrast, 2 weeks after infection, virus infected peripheral blood mononuclear cells were only observed in cats vaccinated with FIV-iscoms + vGR657x15-iscoms or CrFK-iscoms and to a lesser extent in cats vaccinated with FIV-iscoms and vGR657x15-iscoms + FIV-Gag-iscoms, but not in cats vaccinated with SIV-iscoms or PBS. The differences found in cell associated virus loads amongst the respective groups are discussed in the light of antibody mediated enhancement of infectivity and protective effects provided by Gag-specific T cell responses.

Animals↗