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Biomedical subjects

J L Sankalé

Publications and source records attributed to J L Sankalé.

At least 19 recordsLinked to original sources
PubMed2001

Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay.

Evaluation of immune mechanisms responsible for control of viral replication is critical to understanding HIV-2 attenuated biological characteristics in pathogenesis and transmission. Evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed. A simple and rapid anthrax toxin-based ELISPOT method to assess HIV-2 cellular immune response was developed. The modified anthrax toxin-based antigen presentation process performed better than a recombinant vaccinia system and the ELISPOT method significantly enhanced the ease and simplicity of the assay. Using this method, a robust HIV-2 cellular immune response directed toward the p26 core protein was exhibited in 21 of 24 (87.5%) infected women, and all 8 seronegative subjects were negative in both assays. Cellular immune responses were associated with low HIV-2 viral load. This simple and rapid modified anthrax toxin-based ELISPOT method allowed us to demonstrate, strong cellular immune responses that may be critical determinants in the HIV-2 attenuated phenotype.

Antigen Presentation↗
PubMed2000

Interaction with human immunodeficiency virus (HIV) type 2 predicts HIV type 1 genotype.

In West Africa, India, and certain regions of Europe, both human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) are known to cocirculate. To investigate the HIV-1 subtypes involved in dual HIV-1 and HIV-2 infections, we sequenced the envelope C2-V3 region from 29 dually infected female commercial sex workers from Senegal. The majority of women (23 of 29) were infected by HIV-1 subtype A. Within the HIV-1 subtype A sequences, 14 of 23 (60.8%) clustered with the West African associated A/G recombinant form (IbNG), and 9 of 23 (39.2%) formed a separate cluster distinct from the A/G IbNG. In contrast, in HIV-1 singly infected individuals, non-IbNG subtype A was found in only 13 of 98 (13.3%). Therefore, the lack of protection and/or interaction with HIV-2 was associated with a distinct HIV-1 A genotype. These results suggest differences in the biological properties of HIV-1 genotypes and their in vivo interaction with HIV-2.

Amino Acid Motifs↗
PubMed2000

Genetic analysis of HIV type 2 in monotypic and dual HIV infections.

A significant level of genetic variation among HIV-1 and HIV-2 has been described. The interaction of specific HIV-2 subtypes with HIV-1 may serve to identify potential biological properties associated with dual infection. To genetically characterize the HIV-2 strains circulating in Senegal and their relationship to coinfection with HIV-1, we sequenced the HIV-2 envelope C2-C3 region of 12 subjects coinfected with HIV-1 and HIV-2 and 9 subjects singly infected with HIV-2. The phylogenetic analysis showed that all subjects were infected with HIV-2 subtype A, confirming its predominance in West Africa. We did not observe specific sequences or genetic clustering based on coinfection status.

Base Sequence↗
PubMed2000

Molecular epidemiology of genital Chlamydia trachomatis infection in high-risk women in Senegal, West Africa.

The prevalence and heterogeneity of Chlamydia trachomatis infections in a cohort of female sex workers in Dakar (Senegal) were determined by using endocervical-swab-based PCR DNA amplification assays. The overall prevalence of cervical chlamydial infection was 28.5% (206 of 722), and most of these infections were asymptomatic. An increased number of sexual partners was significantly associated with infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.06 to 1.77), while the presence of a yeast infection was negatively associated with chlamydial infection (AOR = 0.28; 95% CI = 0.10 to 0.83). Six different C. trachomatis genotypes were identified based on phylogenetic analysis of the omp1 gene sequences. Interestingly, genotype E predominated (47.6%) and was not associated with visible signs of cervical inflammation compared to non-E genotypes (P < 0.05). Overall, the high rate of asymptomatic C. trachomatis infection by genotype E may suggest genotype-specific properties that confer a transmission advantage in this high risk population.

Adult↗
PubMed1999

V3 serotyping of HIV-1 infection: correlation with genotyping and limitations.

HIV-1 V3 serotyping is a classification of immunodeficiency viruses based on antibody binding to V3 peptides that allows obtaining information on circulating subtypes that could be important for population-based epidemiologic studies. Recently, several laboratories have developed V3 enzyme-immunoassays (EIAs) using V3 peptides of subtypes A to E. In the present study, the utility of including additional peptides of subtypes F to H to the EIA was evaluated on a panel of 203 well-characterized serum samples from patients with diverse geographic origins (22 countries) and known HIV-1 genotype (79 A, 61 B, 21 C, 7 D, 7 E, 21 F, 6 G, 1 H). The results indicate a high predictive value (ppv) for serotypes B (> or =0.86), D (1) and E (0.88), and confirm the difficulty of predicting genotype A or C based on serotype A or C. Results also indicate that inclusion of the F peptide in the V3 EIAs may be useful (ppv = 0.61), but introduction of peptides G and H failed to demonstrate significant sensitivity or specificity for these subtypes. Correlation between serotyping and amino-acid sequences of the V3 region from 103 samples allowed the identification of key amino-acids that appear essential for subtype-specific seroreactivity.

Amino Acid Sequence↗
PubMed1999

Human immunodeficiency virus type 1 subtypes differ in disease progression.

At least 10 different genetic human immunodeficiency virus type 1 (HIV-1) subtypes (A-J) are responsible for the AIDS pandemic. Much of the understanding of HIV-1 disease progression derives from studies in the developed world where HIV infection is almost exclusively subtype B. This has led many to question whether the properties and consequences of HIV-1 infection can be generalized across subtypes that afflict the majority of infected persons in the developing world. From 1985 to 1997, a prospective study of registered female sex workers in Senegal tracked the introduction and spread of HIV-1 subtypes A, C, D, and G. In clinical follow-up, the AIDS-free survival curves differed by HIV-1 subtype. Women infected with a non-A subtype were 8 times more likely to develop AIDS than were those infected with subtype A (hazard ratio=8.23; P=. 009), the predominant subtype in the study. These data suggest that HIV-1 subtypes may differ in rates of progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Genetic characterization of viral quasispecies in blood and cervical secretions of HIV-1- and HIV-2-infected women.

We evaluated cervical samples from 11 HIV-1- and 25 HIV-2-infected individuals. The rate of viral shedding was 36.4% for HIV-1 and 16% for HIV-2, after repeat PCRs. We sequenced multiple clones of the C2-C3 env region from cervical secretions and PBMC samples from three HIV-2-infected individuals, and the C2-V3 env region from four HIV-1-infected individuals. In most cases, phylogenetic analysis showed that the viral sequences from blood and genital secretions were intermingled and subclusters did not segregate according to sample site. In rare cases, however, tissue-specific sequences were observed, suggesting a complex relationship between quasispecies in the two sites where preferential transmission of HIV variants may be due to multiple factors.

Adult↗
PubMed1998

Antibodies to the HIV type 2 core protein p26 and Vpx: association with disease progression.

A longitudinal cohort study was conducted to define the prevalence and temporal pattern of antibody response to the HIV-2 virion-associated proteins p26gag and Vpx. One hundred and forty-one asymptomatic HIV-2-infected women were enrolled, and followed for up to 11 years. Eighty-one percent of the subjects had antibodies to p26, and 51% to Vpx; response to these two antigens was not correlated. The response to both proteins was determined early in infection, and remained stable over time. The absence of antibodies to p26 was a highly significant predictor of CDC category IV HIV-related disease (p < 0.01) in both univariate and multivariate analysis. Antibody response to Vpx alone was not associated with disease progression. However, those individuals lacking anti-p26 antibodies, and with anti-Vpx antibodies, were six times more likely to be classified as CDC category IV by the end of the study (p < 0.01). This represents the first identification of virus-specific serological markers for HIV-2-related disease progression.

Amino Acid Sequence↗
PubMed1998

HIV-1 and HIV-2 dual infection: lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts.

OBJECTIVE: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile. METHODS: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization. RESULTS: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (Pvalue = 0.04). CONCLUSION: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.

Blotting, Southern↗
PubMed1997

Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: implications for vaccine development.

Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine. Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine. The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine. An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic. In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus. Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs. We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.

Amino Acid Sequence↗
PubMed1996

Distinct quasi-species in the blood and the brain of an HIV-2-infected individual.

Sequences of the HIV-2 envelope C2-C3 region were obtained after direct PCR amplification of proviral DNA from the brain and peripheral blood mononuclear cells of an HIV-2-infected AIDS patient. Tissue-specific sequences confirmed previous observations that HIV-2 is indeed present in the central nervous system of infected individuals. Distinct but related quasi-species were present in these two different tissues of the same individual. Residues at position 18 and 19 of the V3 loop and overall charge of the loop suggest that the brain virus was NSI/macrophage tropic; whereas the sequences from the two blood samples were indicative of a SI/T-cell tropic virus. This is the first description of these two genotypes in the same HIV-2-infected individual. Analysis of more samples from different compartments would help to better understand tissue-specific factors in quasi-species evolution in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Natural protection against HIV-1 infection provided by HIV-2.

Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.

AIDS Vaccines↗
PubMed1995

Intrapatient variability of the human immunodeficiency virus type 2 envelope V3 loop.

Studies of HIV-2 infection have shown lower rates of sexual and perinatal transmission and a prolonged incubation period to AIDS as compared to HIV-1. To evaluate the role of genetic variation in HIV pathogenesis, we studied intrapatient variability in the V3 loop of the HIV-2 envelope gene over time in five seropositive individuals. Proviral sequences derived from uncultured PBMC DNA (n = 102) demonstrated an average sequence heterogeneity within a sample of 1.4% (0-4.1%). This was significantly lower than the V3 sequence heterogeneity observed in HIV-1, which can be as high as 6.1%. In HIV-2-seropositive healthy patients the average intrapatient nucleotide variability rate was 0.6% compared to 2.0% in patients with clinical AIDS. The lower rate of variability between HIV-2 and HIV-1 is compatible with differences in transmission and pathogenesis of these two related viruses.

Amino Acid Sequence↗
PubMed1994

Slower heterosexual spread of HIV-2 than HIV-1.

Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985, we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1.11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1.4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses' infectivity potential.

Adult↗
PubMed1992

Prevalence and risk determinants of human immunodeficiency virus type 2 (HIV-2) and human immunodeficiency virus type 1 (HIV-1) in west African female prostitutes.

The authors studied the prevalence and risk determinants for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in female prostitutes from Dakar (1985-1990), Ziguinchor (1987-1990), and Kaolack (1987-1990), Senegal, West Africa. Each cohort showed a distinct distribution of HIVs: 10.0% HIV-2 and 4.1% HIV-1 in Dakar, 38.1% HIV-2 and 0.4% HIV-1 in Ziguinchor, and 27.4% HIV-2 and 1.3% HIV-1 in Kaolack. In 1,275 female prostitutes from Dakar, increase years of sexual activity and a history of scarification were associated with HIV-2 seropositivity. In contrast, HIV-1 seroprevalence was associated with a shorter duration of prostitution and a history of hospitalization. In 278 female prostitutes from Ziguinchor, HIV-2 seroprevalence was associated with women of Guinea-Bissau nationality and increased years of sexual activity. In 157 female prostitutes from Kaolack, HIV-2 seroprevalence was associated with increased years of sexual activity and a history of never using condoms. The authors also studied the risk determinants for HIV-2 in the 1,280 Senegalese prostitutes pooled from all three sites. Controlling for ethnic group, women from Ziguinchor and Kaolack were more likely to be HIV-2 seropositive as compared with women from the Dakar site. Increased years of sexual activity were associated with HIV-2 seropositivity, while a history of excision and BCG vaccinations decreased the risk of HIV-2 infection.

Adult↗
PubMed1992

Infection due to hepatitis delta virus in Africa: report from Senegal and review.

A review of the literature shows strong variations in the prevalence of hepatitis delta virus (HDV) among Africans seropositive for hepatitis B surface antigen (HBsAg). In Senegal, West Africa, prevalence of antibodies to HDV among asymptomatic HBsAg carriers appears to be linked to regional and/or socioeconomic factors. Antibodies to HDV were found in 22 (47%) of 47 HBsAg-seropositive patients with liver disease who were hospitalized in the main hospital of Dakar and in 4% to 44% of asymptomatic HBsAg carriers. Eight (36%) of 22 patients with liver disease were seropositive for IgM antibodies to HDV, whereas none of 18 asymptomatic subjects were seropositive (P less than .01). According to studies conducted in Europe and the United States, the presence of this marker may constitute support for the argument that HDV plays a role in the development of HBsAg-associated liver diseases in Senegal and, presumably, within the African continent.

Adult↗
PubMedDate not supplied

Relation between HIV-2 proviral load and CD4+ lymphocyte count differs in monotypic and dual HIV infections.

OBJECTIVE: To explore and compare the relations between proviral DNA load and CD4+ lymphocyte counts in both HIV-2 monotypic and HIV dual infection. STUDY DESIGN/METHODS: In Dakar, Senegal, where the HIV-1 and HIV-2 epidemics overlap, serum and peripheral blood mononuclear cell (PBMC) DNA samples were collected from registered female sex workers and hospitalized patients. Sera were evaluated for reactivity to antigens of HIV-1 and HIV-2 by immunoblot; dual reactivity was confirmed with recombinant envelope peptides for HIV-1 and HIV-2. These samples were then subjected to HIV-1 and HIV-2 proviral DNA polymerase chain reaction (PCR). To evaluate the HIV-2 cellular proviral DNA loads, a quantitative competitive PCR (QC-PCR) was developed using nested primers to amplify the gag region of HIV-2. This assay used an internal competitor generated by inserting 25 bp in the first-round PCR target sequence. T-lymphocyte subset counts were estimated by flow cytometry for both HIV-2 monotypic and dually infected persons. RESULTS: 35 HIV-2-infected and 33 dually seroreactive samples were evaluated in this study. The CD4+ lymphocyte counts were similar in both groups, with mean values of 449 +/- 390 cells/mm3 for the HIV-2 monotypic infected persons and 476 +/- 308 cells/mm3 among the dually infected persons. However, the median proviral loads differed significantly, with those in the HIV-2 group ranging from 63.2 to 669.8 copies/10(5) CD4+ cells and demonstrating an inverse correlation with CD4+ lymphocyte count. The HIV dually infected persons showed less variation in viral load, ranging from 9.9 to 43.3 copies/10(5) CD4+ cells. Among the HIV dually infected persons, low HIV-2 proviral load was correlated with low CD4+ lymphocyte counts. CONCLUSIONS: The HIV-2 proviral loads in HIV dually infected persons were significantly lower than those in HIV-2 monotypically infected individuals (P < .0001), despite comparable CD4+ lymphocyte counts. These results suggest that different HIV-2 proviral dynamics prevail in HIV dual infection.

CD4 Lymphocyte Count↗