Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and Nef.
ABSTRACT Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T lymphocyte (CTL) epitopes recognized by the targeted population is critical for HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env-specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag and 1 in Nef, were identified in the study; these regions are conserved across clades, including the African subtype C clade. Three antigenic regions were also found to be recognized by CTLs of the study participants. These regions were not identified as immunodominant regions in studies performed in Africa, which highlights the importance of differential clustering of responses within HIV-1 subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef, and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT assay and CTL epitope-prediction software. Ninety percent of the predicted epitopes were clustered in the conserved immunodominant regions of the Gag and Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The identification of conserved epitopes will be important in the planning of an HIV-1 vaccine strategy for subtype C-affected regions.
SourceAvailable from: Sheela V Godbole[Show abstract] [Hide abstract]
ABSTRACT: The Indian HIV epidemic has not reached the predicted proportions even after more than 25 years since the first case of HIV infection was detected in Chennai. An estimated 2.4 million adults were living with HIV in 2009 and an adult prevalence of HIV was 0.3%. The disease burden is geographically diverse and has spread to rural areas also. HIV viruses circulating in India predominantly belong to HIV-1 subtype C although recombinant strains and HIV-2 infections have been identified. Tuberculosis is the commonest opportunistic infection reported from various parts of the country and HIV-TB co-infection is a public health challenge. Government of India launched free antiretroviral treatment (ART) programme 6 years back which has shown good clinical and immunological response in HIV infected individuals. Though the drug resistance monitoring survey has reported effectiveness of regimen in the programme, adherence remains the key issue for minimizing the drug resistance. In addition to the ongoing prevention efforts, India should be poised to accept and scale up newer preventive tools in a manner acceptable and feasible in our socio-cultural context in order to sustain and consolidate the gains that we have achieved so far.Proceedings of the National Academy of Sciences, India - Section B: Biological Sciences 03/2012; 82(1). DOI:10.1007/s40011-011-0013-x · 0.40 Impact Factor
Dataset: 01-Dr. Ebtekar
Dataset: journal.pone.0022680 Mori CTL