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Biomedical subjects

R Cheingsong-Popov

Publications and source records attributed to R Cheingsong-Popov.

At least 37 records · Page 2Linked to original sources
PubMed1994

Serotyping HIV type 1 by antibody binding to the V3 loop: relationship to viral genotype. WHO Network for HIV Isolation and Characterization.

We have investigated whether peptides representing the HIV-1 principal neutralization domain (V3) can be used as antigens in antibody-binding assays to predict the genotypes of the subjects' virus. Serum samples collected from HIV-1-infected subjects from the four WHO-sponsored vaccine evaluation sites (Uganda, Rwanda, Thailand, and Brazil) were characterized by antibody binding to a panel of synthetic V3 peptides that were derived from the consensus sequences of the V3 region of the HIV-1 subgroups according to the env phylogenetic analysis (A-E). An indirect V3 peptide-binding assay was used for primary screening, and a V3 peptide antigen-limiting ELISA was then used as a secondary assay to discriminate cross-reactivity if the screening assay was equivocal. In general, V3 peptide serology could predict HIV-1 genotypes. In sera for which the genotype of the virus was known, peptide assays could predict the correct genotype in approximately 90% of cases for genotypes A, B, C, and E; Ugandan sera of genotype D were more broadly reactive. There was considerable serological cross-reactivity between some HIV-1 genotypes, in particular between A and C, and, to a lesser extent, B and D subtypes. Owing to polymorphism at the crown of the V3 loop, an additional B peptide (B') was required to type Brazilian B genotype sera. These simple assays may help facilitate the determination and distribution of HIV-1 genotypes circulating in populations.

AIDS Vaccines↗
PubMed1994

Identification of an env G subtype and heterogeneity of HIV-1 strains in the Russian Federation and Belarus.

OBJECTIVE: To identify HIV-1 envelope sequence subtypes in infected individuals from the Russian Federation and Belarus. PATIENTS: A cohort of children infected after exposure to non-sterile needles during the 1988-1989 HIV-1 epidemic in southern Russia (n = 20) and HIV-1-seropositive individuals from Russia (n = 1) and Belarus (n = 7) infected via sexual transmission. METHODS: DNA samples derived from peripheral blood mononuclear cells were analysed for their HIV-1 genotypes by the heteroduplex mobility assay (HMA). The 1.3 kilobase-pair env gene fragments encoding a portion of gp120 were amplified by nested polymerase chain reaction, cloned and sequenced. The env sequences derived from these patients were aligned and phylogenetic neighbour-joining and maximum parsimony-derived trees generated. RESULTS: The env sequences derived from eight individuals infected in Russia and Belarus belong to subtype A (one), B (four), C (two), and D (one). Sequences derived from children, infected during parenteral manipulations in southern Russia, and one mother were closely related, but highly divergent, as a group, from all prototypic strains (genetic divergence, 17.2-22.9%). However, they clustered together with env sequences of the V1525 and LBV21-7 isolates from Gabon, recently described to be members of a new HIV-1 env subtype G. CONCLUSION: Extensive heterogeneity of HIV-1 subtypes was evident in the Russian Federation and Belarus. Our data also support the existence of an HIV-1 env genetic subtype G, and such isolates are now apparently present on both the African and European continents. These variants were identified through V3 peptide enzyme-linked immunosorbent assay screening and subsequent HMA analysis. The combination of these techniques represents a model for screening HIV variants within a large population.

Amino Acid Sequence↗
PubMed1994

Molecular epidemiology of HIV-1 in the former Soviet Union: analysis of env V3 sequences and their correlation with epidemiologic data.

OBJECTIVE: To investigate the HIV-1 V3 sequence diversity in the former Soviet Union in 30 subjects infected with HIV-1 via different modes of transmission. PATIENTS: A cohort of children infected after exposure to nonsterile needles during the epidemic in 1988-1989 in southern Russia (Elista, n = 12 and Rostov-on-Don, n = 10), and eight HIV-seropositive subjects from Belarus (Minsk), infected via sexual (n = 7) and parenteral (n = 1) infection. METHODS: The HIV-1 V3 encoding region was amplified by nested polymerase chain reaction on DNA of primary peripheral blood mononuclear cells collected from the study subjects and then cloned and sequenced. RESULTS: The alignment of 127 V3 sequences from 22 patients in the cohort group demonstrated common consensus sequences in both the Elista and Rostov samples. The average means of interperson variation were 5.9 and 6.6% in Elista and Rostov subjects, respectively, and comparable to the mean intraperson variation. The average mean interperson variation between nucleotide sequences of HIV patients infected through sexual transmission was considerably higher (14.9%). CONCLUSION: V3 sequence analysis confirms the epidemiologic data which support the transmission of HIV-1 in children from a single source, and suggests the infection of a mother from her parenterally infected child. Furthermore, the genetic variability of HIV-1 V3 in the noncohort group was particularly divergent indicating the heterogeneity of the virus circulating in the former Soviet Union.

Adolescent↗
PubMed1993

Identification of human immunodeficiency virus type 1 subtypes and their distribution in the Commonwealth of Independent States (Former Soviet Union) by serologic V3 peptide-binding assays and V3 sequence analysis.

Serologic V3 loop peptide-binding assays have been used to predict divergent human immunodeficiency virus type 1 (HIV-1) strains from the Commonwealth of Independent States (former Soviet Union) that have been subsequently confirmed by sequencing of the V3 region. Initial screening was done by MN V3 peptide binding; 12 parenterally infected HIV-1-positive subjects from Elista and Rostov (group 1) with low-titer MN binding and 6 heterosexually infected HIV-1-positive adults from Byelorussia (group 2) with high-titer MN binding were selected. A consensus sequence from the Elista and Rostov areas was generated; a corresponding 14-mer peptide was synthesized and used in an indirect ELISA to screen sera from 392 individuals from diverse geographic areas. Reactivity to the consensus peptide was 82% in subjects from the homologous areas and 11%-38% in other areas. Antibody binding to a panel of synthetic V3 peptides may be used to predict the presence of diverse strains of HIV-1 within virally heterogenous populations.

Amino Acid Sequence↗
PubMed1993

Immunization of human HIV-seronegative volunteers with recombinant p17/p24:Ty virus-like particles elicits HIV-1 p24-specific cellular and humoral immune responses.

OBJECTIVE: To evaluate the immune response to HIV-1 p24 generated in vivo by p17/p24:Ty virus-like particles (p17/p24:Ty-VLP) by examining the lymphoproliferative and antibody (Ab) responses to HIV-1 p24, as well as Gag-specific cytotoxic T lymphocytes (CTL), in HIV-seronegative volunteers immunized with hybrid p17/p24:Ty-VLP. DESIGN AND METHODS: Sixteen HIV-seronegative volunteers were immunized with p17/p24:Ty-VLP at two dose levels (100 or 500 micrograms) and monitored for the following 48 weeks for production of anti-p24 and anti-p17 Ab, in vitro lymphoproliferative responses to HIV-1 p24 and p17, and in vitro CTL responses to HIV-1 Gag. RESULTS: Twelve out of the 16 volunteers had significant p24-specific proliferative responses, with volunteers on the higher dose schedule exhibiting earlier proliferative responses than those on the lower dose schedule. Proliferative responses in both volunteer groups were similar in overall magnitude but appeared at different times during the immunization schedule. Anti-p24 Ab were detected in six out of the nine individuals in the lower dose group and in five out of the seven in the higher dose group. There was a good correlation between the presence of p24-specific Ab and the detection of lymphoproliferative responses to the p24 protein in peripheral blood mononuclear cells isolated from the same individuals. Anti-p17 Ab were detected in five volunteers. No Gag-specific CTL responses were detected. CONCLUSION: We conclude that hybrid HIV-1 p17/p24:Ty-VLP are capable of inducing both cellular and humoral immunity to HIV-1 Gag p17 and p24 components and are worthy of further study as a potential HIV immunotherapeutic.

AIDS Vaccines↗
PubMed1992

Geographic diversity of human immunodeficiency virus type 1: serologic reactivity to env epitopes and relationship to neutralization.

The antibody recognition of the major neutralization epitopes of human immunodeficiency virus type 1 (HIV-1) in 829 HIV-1-seropositive subjects from North America (106), Europe (241), Africa (342), and Asia (100) was investigated. Peptides derived from diverse published V3 loop sequences were used as antigen, and serum reactivity was detected by sensitive ELISAs. Antibody binding to peptides derived from the V3 loop sequence of HIV-1 isolates varies considerably depending on the geographic origin of the antibody and is associated with neutralization titer against homologous isolates. Serotype reactivity to peptides may be a simple and rapid approach to investigation of HIV-1 env diversity worldwide and may assist the choice of immunogen for development of future AIDS vaccines.

Africa↗
PubMed1992

Development of HIV-1 group-specific neutralizing antibodies after seroconversion.

OBJECTIVE: To study the induction of group-specific (gs) neutralizing antibodies to HIV-1 after seroconversion. DESIGN AND METHODS: Serum samples taken sequentially from seven Dutch homosexual men and four British haemophiliacs (anonymous sample, therefore sex not known) before and after seroconversion were tested for neutralizing antibodies effective against five diverse HIV-1 strains. Strains of HIV-1 tested included isolates from the United States, Europe and Africa. RESULTS: The gs neutralizing antibody response varied between individuals. Only five of the 11 individuals studied produced detectable neutralizing antibodies to laboratory-adapted HIV-1 strains (for example, IIIB) within 32 weeks of seroconversion. Most individuals initially produced antibodies effective against US/European isolates; the response then generally broadened to include the more diverse strains, i.e., African. CONCLUSIONS: These results suggest that the gs neutralizing target for HIV-1 is poorly immunogenic in vivo and is probably not highly conserved among diverse HIV-1 strains.

HIV Antibodies↗
PubMed1991

Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection.

OBJECTIVE: To study the contribution of the humoral response to HIV-I at seroconversion to disease outcome after 84 months. DESIGN: A retrospective longitudinal study. SETTING: Two haemophilia centres in the United Kingdom. PATIENTS: 88 Haemophiliac patients infected with HIV-I for whom sera were available from before seroconversion and in whom clinical follow up data were available. RESULTS: Kaplan-Meier survival analysis showed a significant difference between a high titre (greater than 1600) p24 antibody response at seroconversion and prolonged time before the development of HIV related disease (p = 0.0008). In contrast, higher titres of antibody to gp120 at seroconversion (greater than 25,600) correlated with more rapid clinical deterioration (p = 0.025). CONCLUSIONS: The first humoral response to HIV proteins at seroconversion is associated with clinical outcome; patients with an initial low titre antibody response to the gagp24 protein have a significantly faster rate of progression to CDC stage IV disease. Patients with a high titre p24 antibody response progress to AIDS more slowly, and these data provide an explanation why p24 antigenaemia is not universally detected in patients with AIDS. It is unclear whether the association between a strong initial p24 antibody response and slower progression of HIV disease is causal and if so whether it is due to viral or host factors.

Gene Products, gag↗
PubMed1991

Comparative humoral responses to HIV-1 p24gag and gp120env in subjects from East Africa and the UK.

We compared 1616 sera from HIV-1-infected subjects and matched HIV-negative local controls in Uganda, Kenya and the UK. Sera were screened for specific antibody to HIV-1 p24 Gag and gp120 Env proteins and for p24 antigenaemia. In contrast to the UK, the majority of African HIV-1-infected subjects maintained detectable anti-p24 antibodies. However, lower reactivity of anti-p24 was observed in African AIDS patients, compared with those with asymptomatic HIV-1 infection. This reduction in anti-p24 reactivity with more advanced clinical stage was less marked in African HIV-1 infection than in the UK. Correspondingly, p24 antigenaemia was more common in patients with AIDS from the UK than in African patients (65 versus 4%). Reductions in anti-gp120 reactivity were observed in African AIDS patients, compared with the asymptomatic group. However, median reactivity of anti-gp120 in UK patients remained unchanged in both asymptomatic and AIDS subjects. The differences in humoral response to p24 and gp120 between Africa and the UK are semi-quantitative rather than qualitative and could be explained by initial higher antibody response to HIV-1 in African subjects.

Cross-Sectional Studies↗
PubMed1990

Antibodies to HIV-1 nef(p27): prevalence, significance, and relationship to seroconversion.

A sensitive and specific enzyme-linked immunoassay for antibodies to the human immunodeficiency virus type 1 (HIV-1) nef gene product, p27, has been developed using recombinant Escherichia coli-derived protein from the LAV-1-Bru sequence. Of 92 HIV-1 infected hemophiliacs, 72 (78%) produced anti-nef antibodies in this assay; the early appearance of anti-nef prior to full seroconversion was a rare event in this population, occurring in only one subject (approximately 1%). Anti-nef antibodies were not detected in any of 500 sera from 98 repeatedly HIV seronegative subjects who had been exposed to sexually transmitted modes of HIV infection (45 subjects) or through blood products (53 subjects). There was no significant association of titer or anti-nef antibody with protection from disease in HIV infection (p = 0.1). Although the nef protein is relatively immunogenic in natural infection, this study cannot confirm the previously reported high prevalence of anti-nef antibodies prior to seroconversion, nor the finding of anti-nef antibodies in HIV seronegative but exposed subjects.

Cohort Studies↗
PubMed1990

Antibodies to a putative HIV gp41 immunosuppressive peptide, pHIVIS (583-599), do not correlate significantly with outcome in HIV infection.

We have studied the prevalence of antibodies to peptides derived from the transmembrane protein of HIV, gp41. Previous work has suggested that the presence of antibodies to the gp41 peptide known as pHIVIS (env 583-599) is associated with protection from immunosuppression in HIV infection. We studied 171 sequential sera from 55 HIV-1-infected people in various clinical stages of disease. There was no significant association between antibodies to pHIVIS and clinical status in this study. Although pHIVIS has sequence similarity to the putative immunosuppressive region of the C-type oncornaviruses (p15E), antibodies to this peptide do not appear to be associated with protection from immunosuppression in natural HIV infection.

Amino Acid Sequence↗
PubMed1987

Decline of anti-p24 antibody precedes antigenaemia as correlate of prognosis in HIV-1 infection.

A cohort of 84 homosexual men presenting with persistent generalized lymphadenopathy (PGL) was studied between March 1982 and March 1987. A progression rate to AIDS of 5% per year was seen in those who were infected with HIV. Certain clinical features and routine laboratory investigations were significantly associated with an increased risk of disease progression, but had only limited predictive value. Two hundred and fifty-two serial sera from 57 patients were analysed for the p24 antigen (Abbott), the principal core protein of HIV and antibody against p24 by direct enzyme-linked immunosorbent assay (ELISA). Patients who remained well retained a high titre of anti-p24 antibody compared with those who progressed to AIDS-related complex (ARC) or AIDS. HIV antigen was detectable in 40% of AIDS patients 2 years before diagnosis, but antigenaemia was preceded by loss of anti-p24 antibody by up to 18 months and preceded AIDS by up to 40 months. ARC patients tended to be negative when tested for both alpha-p24 antibody and antigen, suggesting a transitional state. Analysis of the humoral response against gag proteins appears to correlate closely with clinical status and may be an earlier and more consistent way of predicting disease progression than p24 antigenaemia, or clinical and routine laboratory investigations.

AIDS-Related Complex↗
PubMed1986

HTLV-III antibody and T-cell subset ratios in haemophiliacs and their spouses.

44% of 63 British patients with either haemophilia A or B were HTLV-III antibody positive (HTLV-VIII+). HTLV-III+ was more frequent in high factor VIII concentrate users and 75% of severely affected haemophilia A patients were HTLV-III+. All eight patients who were exposed to factor IX concentrate were HTLV-III-. 17 haemophilia A patients who received only British made factor VIII concentrate (average 12,000 units/year) were HTLV-III-. Two of 63 patients had evidence of a pre-AIDS type symptom complex and both were HTLV-III+. Information from a cohort of 21 Liverpool haemophiliacs suggests that HTLV-III was first introduced into this country in 1981. OKT4/T8 ratios were abnormal in 52% of 21 patients studied but this finding was not confined to either HTLV-III+ or HTLV-III- individuals. The spouses of 14 HTLV-III+ haemophiliacs were all HTLV-III-.

Adolescent↗
PubMed1985

AIDS and haemophilia: morbidity and morality in a well defined population.

One hundred and forty-three multitransfused patients with hereditary haemostatic disorders were examined for evidence of disease related to the acquired immune deficiency syndrome (AIDS). Ninety-nine patients with severe haemophilia A were tested for anti-HTLV-III and 76 were found to be positive. All except one of these seropositive patients had received commercial factor VIII concentrates at some time. Eighteen patients with haemophilia B were tested and all were anti-HTLV-III negative. Three out of 36 sexual partners of patients with haemophilia A positive for anti-HTLV-III were also seropositive. One, who had recently received blood transfusions, had AIDS with Pneumocystis carinii pneumonia. Three patients with severe haemophilia A died from Aids. A further 30 haemophiliacs had AIDS related complex or lymphadenopathy that could be related to HTLV-III infection. There was a significant correlation between lymphadenopathy and anti-HTLV-III seropositivity. No evidence of casual spread of AIDS was found since all 68 health care staff tested were anti-HTLV-III negative, including three surgeons who regularly worked with patients positive for anti-HTLV-III. The resources devoted to counselling and laboratory support in centres treating people at risk and their families need to be urgently reassessed.

Acquired Immunodeficiency Syndrome↗