ABSTRACT
The progression of AIDS depends on the complex host and virus interactions. The most important disease progression hallmarks are immune activation and apoptosis. In this study, we address the prevalence of polymorphisms related to proinflammatory and apoptotic genes, such as IFNG (+874T/A), TNF (308G/A), IL6 (-174G/C), IL8 (-251A/T), FAS (-670A/G), and FASL (-124A/G) in 160 ethnically mixed HIV-1-infected patients from multicentre cohorts with different clinical outcomes (13 elite controllers [EC], 66 slow long-term non-progressors [LTNPs], and 81 progressors [P]). The genotyping was accomplished by TaqMan-qPCR. Among all the polymorphisms analyzed in the cytokines, the IL6 -174G/C polymorphism showed a higher frequency of GG genotype in the LTNP and LTNP+EC groups as compared to the P group. Moreover, there was a significantly higher frequency of the G allele in the LTNP and LTNP+EC groups as compared to the P group. On the other hand, the levels of CD4+ T lymphocytes were higher among individuals showing the AA and AG genotypes for the FASL -124A/G polymorphism as compared to the GG genotype. Furthermore, the AG and AA genotypes were more frequent, as compared to the GG genotype, in individuals showing a lower viral load. In contrast, for the FAS -670A/G polymorphism, a significantly higher viral load was observed in individuals with the AG genotype as compared to the GG genotype. In conclusion, we found three genetic allelic variants of the IL6 -174G/C, FASL -124A/G, and FAS -670A/G polymorphisms that were related to disease progression and immunological and virological markers in cohorts of HIV-1-positive ethnically mixed patients.
Subject(s)
Fas Ligand Protein/genetics , HIV Seropositivity/genetics , HIV Seropositivity/immunology , Interleukin-6/genetics , fas Receptor/genetics , Adult , Disease Progression , Ethnicity , Fas Ligand Protein/immunology , Female , Genetic Predisposition to Disease , Genotype , HIV Seropositivity/ethnology , HIV-1/genetics , HIV-1/immunology , Humans , Interleukin-6/immunology , Male , Middle Aged , Polymorphism, Single Nucleotide , Young Adult , fas Receptor/immunologyABSTRACT
OBJECTIVES: A superior capacity of controlling HIV has been attributed to CD8(+) T cells directed against HIV-Gag compared to Nef, particularly in the context of some protective human leukocyte antigen (HLA) alleles. To further elucidate this protective effect, we compared the multifunctional and differentiation characteristics of CD8(+) T cells specific for HIV-Gag and Nef in HLA-B57/5801-positive and negative nonprogressors. METHODS: A head-to-head comparison of CD8(+) T cells specific for HIV-Gag and Nef frequencies, cytokine production and differentiation was conducted, in 11 HLA-B57/5801 and 11 HLA-B57/5801 HIV-infected individuals selected from a cohort of 53 nonprogressors by using IFN-gamma-ELISpot assay and flow cytometry analysis of intracellular cytokine production and differentiation profile. Correlations with HIV parameters were studied. RESULTS: Frequencies of Gag-specific but not of Nef-specific CD8(+) T cells correlated with peripheral blood mononuclear cell (PBMC)-associated HIV-DNA. The HIV-Gag and Nef-specific CD8(+) T cells did not differ for IL-2 production in either HLA-B57/5801 or HLA-B57/5801 individuals. The IFN-gamma-producing Gag-specific CD8(+) T cells in HLA-B57/5801 individuals significantly differed from their Nef-specific counterparts by displaying higher proportions of central memory CD45RACCR7 cells positive for CD27(+). This differentiation pattern was not observed in HLA-B57/5801 individuals. Only these HLA-B57/5801-positive Gag-specific CD27(+) central memory CD8(+) T cells, but not their Nef-specific counterparts, negatively correlated with cell-associated HIV-DNA. CONCLUSION: HLA-B57/5801 drives a preferential CD27(+) differentiation of central memory CD8(+) T cells directed against HIV-Gag but not Nef that may contribute to the ability of Gag-specific CD8(+) T cells to better control HIV in HLA-B57/5801 nonprogressors.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Genes, gag/genetics , HIV Infections/immunology , HIV-1/genetics , HLA-B Antigens/immunology , nef Gene Products, Human Immunodeficiency Virus/immunology , Cell Separation , DNA, Viral/genetics , Enzyme-Linked Immunosorbent Assay , HIV Infections/genetics , Humans , nef Gene Products, Human Immunodeficiency Virus/geneticsABSTRACT
Malassezia furfur is lypophilic yeast commonly associate with dermatological disorders. In the present work, we described the isolation of 47 M. furfur strains from three groups of patients: pityriasis versicolor (21 isolates), seborrhoeic dermatitis (15 isolates) and seborrhoeic dermatitis of the HIV positive patients (11 isolates). To investigate the identity of the strains at molecular level, DNA genomic of M. furfur strains were prepared and used to RAPD-PCR analyses. RAPD assay were carried out using two decamer primers and bands pattern generated were analyzed by an Unweighted Pair-Group Method (UPGMA). Dendrogram established a distinct differentiation between M. furfur isolates from pityriasis versicolor and seborrhoeic dermatitis patients with or without AIDS. We concluded that RAPD typing presented a high discriminatory power between strains studied in this work and can be applied in epidemiological investigation of skin disease causing by M. furfur.