[show abstract][hide abstract] ABSTRACT: A prospective study of high-risk commercial sex workers in Senegal has shown that HIV-2 infection may reduce the risk of subsequent HIV-1 infection; these findings have been confirmed and extended, now with 13 years of observation. While exploring the biological mechanisms behind this natural protection, we found that a significant proportion of peripheral blood mononuclear cells obtained from HIV-2-infected subjects resisted in vitro challenge with CCR5-dependent HIV-1 viruses but not CXCR4-dependent viruses. High levels of beta-chemokines, the natural ligands of the CCR5 coreceptor, were correlated with low levels of viral replication, and resistance was abrogated by antibodies to beta-chemokines. Our results suggest that beta-chemokine-mediated resistance may be an important correlate of HIV protection against HIV-1 infection and relevant to HIV vaccine design.
Proceedings of the National Academy of Sciences 07/2000; 97(12):6797-802. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Levels of virus in the plasma are closely related to the pathogenicity of human immunodeficiency virus type 1 (HIV-1). HIV-2 is much less pathogenic than HIV-1, and infection with HIV-2 leads to significantly lower plasma viral load. To identify the source of this difference, we measured both viral RNA and proviral DNA in matched samples from 34 HIV-2-infected individuals. Nearly half had undetectable viral RNA loads (<100 copies/ml), but levels of proviral DNA were relatively high and confirmed that quantities of provirus in HIV-1 and HIV-2 infection were similar. Overall, HIV-2 proviral DNA load did not correlate with viral RNA load, and higher viral RNA load was associated with increased production of plasma virus from the proviral template. These results suggest that low viral load in HIV-2 infection is due to decreased rates of viral production, rather than differences in target cell infectivity.
Journal of Virology 03/2000; 74(3):1554-7. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV type 1 (HIV-1), but the mechanisms underlying this difference have not been defined. We developed an internally controlled quantitative reverse transcriptase-polymerase chain reaction to measure HIV-2 viral load and determined levels of plasma virus in a cohort of registered commercial sex workers in Dakar, Senegal. The assay has a lower limit of detection of 100 copies/mL and is linear over 4 logs. HIV-2 viral RNA was detectable in 56% of all samples tested; the median load was 141 copies/mL. Levels of viral RNA in the plasma were inversely related to CD4+ cell counts. HIV-2 and HIV-1 viral loads were compared among the seroincident women in the cohort; the median viral load was 30x lower in the HIV-2-infected women (P<.001, Wilcoxon rank sum test), irrespective of the length of time infected. This suggests that plasma viremia is linked to the differences in the pathogenicity of the 2 viruses.
The Journal of Infectious Diseases 10/1999; 180(4):1116-21. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
The Journal of Infectious Diseases 02/1999; 179(1):68-73. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
AIDS Research and Human Retroviruses 12/1998; 14(16):1473-81. · 2.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
AIDS Research and Human Retroviruses 06/1995; 11(5):617-23. · 2.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study examines the prevalence and risk factors for Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) infection in pregnant women in Dakar, Senegal. From April 1991 to January 1993, 9,518 pregnant women were interviewed and serologically tested for antibodies to HIV-1 and HIV-2; 26 (0.3%) were HIV-1 seropositive, 44 (0.5%) were HIV-2 seropositive, two (0.02%) were dually seropositive, and 9,448 (99.3%) were seronegative. Guinea-Bissau nationality and age > 25 years were associated with HIV-2 infection, whereas parity < or = 2 was associated with HIV-1 infection. Among women who gave birth to live infants, shorter length of union with the partner and having been married more than once were associated with HIV-2 infection, whereas age < or = 25 years was associated with HIV-1 infection. Information gained by this study may help target intervention strategies for preventing maternal HIV infection and understanding biological differences between the two viruses.
Journal of acquired immune deficiency syndromes 08/1994; 7(7):711-7.
[show abstract][hide abstract] ABSTRACT: Of 45 individuals seropositive for human T cell lymphotropic virus type III/lymphadenopathy-associated virus, 45 were found to have detectable salivary antibodies to viral antigens by a radioimmunoprecipitation assay. The results also showed that a Western blot assay for salivary antibodies may be possible. The feasibility of a diagnostic test for human T cell lymphotropic virus type III/lymphadenopathy-associated virus not requiring venipuncture is discussed.
Journal of Clinical Microbiology 12/1986; 24(5):873-5. · 4.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transmission of the human immunodeficiency virus (HIV) was studied in a group of patients with cancer who received transfusion of blood components harvested from a single, asymptomatic, seropositive donor. Of ten living recipients, nine had antibodies to the virus in fresh or cryopreserved sera at a median of 384 days (range, 237 to 686) after transfusion. In three patients, an enzyme-linked immunosorbent assay was negative at the same time that Western blot and radioimmunoprecipitation techniques showed seropositivity. Cultures for HIV obtained at a median of 615 days (range, 322 to 714) after transfusion were positive in seven of nine seropositive recipients. Six seropositive recipients have developed immunologic and clinical sequelae of HIV infection at a median of 286 days (range, 56 to 745) after transfusion. The sera of the two patients without clinical sequelae neutralized HIV in an in-vitro assay, whereas the seven other seropositive patients lacked such neutralizing antibodies. Our study characterizes the clinical, serologic, virologic, and immunologic manifestations of HIV infection in immunocompromised persons.
Annals of internal medicine 11/1986; 105(4):519-27. · 13.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Selected populations of cats that were naturally exposed to the feline leukemia virus (FeLV) were found to have humoral antibodies to a normal cell protein designated NCP105. Earlier studies revealed that cats exposed to FeLV often had serum antibodies to the feline oncornavirus-associated cell membrane (FOCMA) as well as to a feline sarcoma virus (FeSV) -specific transforming protein designated gag-fes. Cats with no history of exposure to FeLV or FeSV lacked antibodies to all three antigens: NCP105, FOCMA, and gag-fes. Following exposure to FeLV, cats develop antibodies to either NCP105 or to gag-fes and FOCMA, but not to both groups of antigens. NCP105 is present in both normal and transformed cells from a wide variety of species. It lacks peptide homology with gag-fes and it is not a phosphoprotein. The presence of antibodies to NCP105 in cats exposed to FeLV but not in unexposed cats suggests that FeLV may activate the NCP105 gene or increase the relative immunogenicity of this protein in vivo.
Cancer Investigation 02/1984; 2(2):81-90. · 2.24 Impact Factor