PMID- 23824804 OWN - NLM STAT- MEDLINE DCOM- 20131106 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 18 DP - 2013 Sep TI - Evolutionarily conserved epitopes on human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus reverse transcriptases detected by HIV-1-infected subjects. PG - 10004-15 LID - 10.1128/JVI.00359-13 [doi] AB - Anti-human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL)-associated epitopes, evolutionarily conserved on both HIV type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptases (RT), were identified using gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISpot) and carboxyfluorescein diacetate succinimide ester (CFSE) proliferation assays followed by CTL-associated cytotoxin analysis. The peripheral blood mononuclear cells (PBMC) or T cells from HIV-1-seropositive (HIV(+)) subjects were stimulated with overlapping RT peptide pools. The PBMC from the HIV(+) subjects had more robust IFN-gamma responses to the HIV-1 peptide pools than to the FIV peptide pools, except for peptide-pool F3. In contrast, much higher and more frequent CD8(+) T-cell proliferation responses were observed with the FIV peptide pools than with the HIV peptide pools. HIV-1-seronegative subjects had no proliferation or IFN-gamma responses to the HIV and FIV peptide pools. A total of 24% (40 of 166) of the IFN-gamma responses to HIV pools and 43% (23 of 53) of the CD8(+) T-cell proliferation responses also correlated to responses to their counterpart FIV pools. Thus, more evolutionarily conserved functional epitopes were identified by T-cell proliferation than by IFN-gamma responses. In the HIV(+) subjects, peptide-pool F3, but not the HIV H3 counterpart, induced the most IFN-gamma and proliferation responses. These reactions to peptide-pool F3 were highly reproducible and persisted over the 1 to 2 years of testing. All five individual peptides and epitopes of peptide-pool F3 induced IFN-gamma and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine. FAU - Sanou, Missa P AU - Sanou MP AD - Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA. FAU - Roff, Shannon R AU - Roff SR FAU - Mennella, Antony AU - Mennella A FAU - Sleasman, John W AU - Sleasman JW FAU - Rathore, Mobeen H AU - Rathore MH FAU - Yamamoto, Janet K AU - Yamamoto JK FAU - Levy, Jay A AU - Levy JA LA - eng GR - UL1 RR029890/RR/NCRR NIH HHS/United States GR - R01 AI030904/AI/NIAID NIH HHS/United States GR - P30 AI027763/AI/NIAID NIH HHS/United States GR - R01 AI065276/AI/NIAID NIH HHS/United States GR - R01-AI30904/AI/NIAID NIH HHS/United States GR - R01-AI65276/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130703 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Epitopes) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.7.49 (RNA-Directed DNA Polymerase) SB - IM MH - Adult MH - Aged MH - Animals MH - Cell Proliferation MH - Conserved Sequence MH - Enzyme-Linked Immunospot Assay MH - Epitopes/genetics/*immunology MH - Female MH - HIV-1/genetics/*immunology MH - Humans MH - Immunodeficiency Virus, Feline/genetics/*immunology MH - Interferon-gamma/metabolism MH - Leukocytes, Mononuclear/immunology MH - Male MH - Middle Aged MH - RNA-Directed DNA Polymerase/genetics/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Young Adult PMC - PMC3754003 EDAT- 2013/07/05 06:00 MHDA- 2013/11/07 06:00 PMCR- 2014/03/01 CRDT- 2013/07/05 06:00 PHST- 2013/07/05 06:00 [entrez] PHST- 2013/07/05 06:00 [pubmed] PHST- 2013/11/07 06:00 [medline] PHST- 2014/03/01 00:00 [pmc-release] AID - JVI.00359-13 [pii] AID - 00359-13 [pii] AID - 10.1128/JVI.00359-13 [doi] PST - ppublish SO - J Virol. 2013 Sep;87(18):10004-15. doi: 10.1128/JVI.00359-13. Epub 2013 Jul 3.