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Titolo:
INTRACELLULAR EXPRESSION OF CELLULAR EIF-5A MUTANTS INHIBITS HIV-1 REPLICATION IN HUMAN T-CELLS - A FEASIBILITY STUDY
Autore:
JUNKER U; BEVEC D; BARSKE C; KALFOGLOU C; ESCAICH S; DOBROVNIK M; HAUBER J; BOHNLEIN E;
Indirizzi:
SYSTEMIX INC,PROGENESYS PROGRAM,3155 PORTER DR PALO ALTO CA 94304 SYSTEMIX INC,PROGENESYS PROGRAM PALO ALTO CA 94304 SANDOZ GMBH,DEPT IMMUNODERMATOL A-1235 VIENNA AUSTRIA
Titolo Testata:
Human gene therapy
fascicolo: 15, volume: 7, anno: 1996,
pagine: 1861 - 1869
SICI:
1043-0342(1996)7:15<1861:IEOCEM>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSDOMINANT NEGATIVE FORM; REV ACTIVATION DOMAIN; RETROVIRAL VECTORS; REGULATORY PROTEINS; GENE-TRANSFER; VIRUS; INITIATION; SEQUENCE; AIDS; LYMPHOCYTES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
U. Junker et al., "INTRACELLULAR EXPRESSION OF CELLULAR EIF-5A MUTANTS INHIBITS HIV-1 REPLICATION IN HUMAN T-CELLS - A FEASIBILITY STUDY", Human gene therapy, 7(15), 1996, pp. 1861-1869

Abstract

Previously, we described two mutants of the cellular Rev co-factor, eukaryotic initiation factor 5A (eIF-5AM13 and M14), which suppress human immunodeficiency virus type 1 (HIV-1) SF2 replication in clonal T cell lines. This study introduced the notion that it is possible to develop gene therapies against infectious agents on the basis of mutant host factors required for viral replication. In this report, we providefurther evidence to support this new paradigm and describe murine leukemia virus (MLV)-based retroviral vectors expressing three different eIF-5A mutants from the viral long terminal repeat (LTR). HIV-1 replication (SF2, HXB-3) was reduced up to 2 orders of magnitude in transduced, polyclonal T cell populations. All eIF-5A mutants also showed antiviral activity (similar to seven-fold reduction) in a chronic HIV-1 infection model. Expression of eIF-5A mutant M13 Delta in peripheral blood lymphocytes (PBLs) showed no difference in proliferation and metabolic activity as determined in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-assay, suggesting that expression of this type of mutant protein is not associated with cellular toxicity. In summary, these data suggest that gene therapy for HIV-1 infection can be developed on the basis of mutants of the Rev co-factor eIF-5A.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/08/20 alle ore 23:29:30