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Titolo:
HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE MUTANTS RETAIN IN-VITROINTEGRASE ACTIVITY YET FAIL TO INTEGRATE VIRAL-DNA EFFICIENTLY DURINGINFECTION
Autore:
LEAVITT AD; ROBLES G; ALESANDRO N; VARMUS HE;
Indirizzi:
513 PARNASSUS AVE,ROOM S-577,BOX 0100 SAN FRANCISCO CA 94143 UNIV CALIF SAN FRANCISCO,DEPT LAB MED SAN FRANCISCO CA 94143 UNIV CALIF SAN FRANCISCO,DEPT INTERNAL MED SAN FRANCISCO CA 94143 UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL SAN FRANCISCO CA 94143
Titolo Testata:
Journal of virology
fascicolo: 2, volume: 70, anno: 1996,
pagine: 721 - 728
SICI:
0022-538X(1996)70:2<721:HTIMRI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
MURINE LEUKEMIA-VIRUS; HIV-1 INTEGRASE; ESCHERICHIA-COLI; RETROVIRAL DNA; PROTEIN; INVITRO; DOMAINS; SEQUENCES; CLEAVAGE; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
A.D. Leavitt et al., "HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE MUTANTS RETAIN IN-VITROINTEGRASE ACTIVITY YET FAIL TO INTEGRATE VIRAL-DNA EFFICIENTLY DURINGINFECTION", Journal of virology, 70(2), 1996, pp. 721-728

Abstract

The viral integrase (IN) protein is the only viral protein known to be required for integration of the human immunodeficiency virus type 1 (HIV-1) genome into the host cell DNA, a step in the viral life cycle that is essential for viral replication, To better understand the relationship between in vitro IN activity and IN-mediated integration of viral DNA in an infected cell, we characterized the effects of 13 IN mutations on viral replication in cultured cells, Using HIV-1 genomes that express the hygromycin resistance gene and do not express the HIV-1env gene, we generated stocks of pseudotype virus coated with the murine leukemia virus amphotropic envelope glycoprotein, containing either wild-type or mutant HIV-1 IN, All mutants produced normal amounts ofphysical particles, as measured by reverse transcriptase activity andcapsid protein (p24) concentration, but they formed three groups based on infectious titer and synthesis of viral DNA, Changes at the threehighly conserved acidic residues in the IN core domain (D-64, D-116, and E-152) impair provirus formation without affecting viral DNA synthesis or the accumulation of viral DNA in the nucleus of the infected cell, a phenotype predicted by each mutant's lack of in vitro integraseactivity, Mutations at positions N-120, R-199, and W-235 minimally affect in vitro integrase activity, but infectious titers are severely reduced, despite normal synthesis of viral DNA, implying a defect during integration in vivo. Mutations in the zinc binding region (H12C, H16V, and H16C), S81R, and a deletion of residues 32 through 275 yield noninfectious particles that synthesize little or no viral DNA followinginfection, despite wild-type levels of reverse transcriptase activityand viral RNA in the particles, The two latter classes of mutants suggest that IN can affect DNA synthesis or integration during infection in ways that are not appreciated from currently used assays in vitro.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 22:33:48