title: Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
abstract: Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short-term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects. IFNγ-ELISpot and CFSE-proliferation analyses were performed with PBMC using overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either IFNγ or T-cell proliferation analysis. PBMC and T cells from infected subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool (Fp14) by IFNγ production and one additional FIV p24 peptide pool (Fp9) by T-cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV peptide pools were highly reproducible and persisted throughout 2-4 y of monitoring. Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a. Selected FIV and corresponding SIV epitopes recognized by HIV-1 infected patients indicate that these protein sequences are evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes, which could be used as a vaccine for prophylaxis or immunotherapy.
authors.affiliation: a Department of Infectious Diseases and Pathology; College of Veterinary Medicine; University of Florida ; Gainesville , FL , USA.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Roff
authors.forename: Missa P
authors.initials: MP
authors.lastname: Sanou
authors.forename: Mobeen H
authors.initials: MH
authors.lastname: Rathore
authors.forename: Jay A
authors.initials: JA
authors.lastname: Levy
authors.forename: Janet K
authors.initials: JK
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D049109:Cell Proliferation; D003429:Cross Reactions; D058501:Enzyme-Linked Immunospot Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D014758:Viral Core Proteins; D007371:Interferon-gamma
keywords: AIDS, acquired immune deficiency syndrome; ART, anti-retroviral therapy; CFSE, Carboxyfluorescein succinimidyl ester; CMI, cell mediated immunity; CTL epitopes; CTL, cytotoxic T cell; FIV p24; FIV, feline immunodeficiency virus; GrzA, granzyme A; GrzB, granzyme B; HERV, human endogenous retrovirus; HIV p24; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; ICS, intracellular staining; LANL, Los Alamos National Laboratory; LTS, Long term survivors; Nab, broadly neutralizing antibody; PHA, phytohaemagglutinin; SFU, spot forming units; SIV p24; SIV, simian immunodeficiency virus; ST, short term survivors; aa, amino acid; feline immunodeficiency virus; vaccine epitopes
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