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Titolo:
HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) PROTEIN VIF INHIBITS THE ACTIVITY OF HIV-1 PROTEASE IN BACTERIA AND IN-VITRO
Autore:
KOTLER M; SIMM M; ZHAO YS; SOVA P; CHAO W; OHNONA SF; ROLLER R; KRACHMAROV C; POTASH MJ; VOLSKY DJ;
Indirizzi:
COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,COLL PHYS & SURG,MOL VIROL LAB,432 W 58TH ST NEW YORK NY 10019 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MOL GENET IL-91010 JERUSALEM ISRAEL COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,COLL PHYS & SURG,MOL VIROL LAB NEW YORK NY 10019
Titolo Testata:
Journal of virology
fascicolo: 8, volume: 71, anno: 1997,
pagine: 5774 - 5781
SICI:
0022-538X(1997)71:8<5774:HT(PVI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESCHERICHIA-COLI; INFECTED-CELLS; HTLV-III/LAV; SOR GENE; VIRAL INFECTIVITY; FUSION PROTEINS; T-LYMPHOCYTES; DNA-SYNTHESIS; GAG PROTEINS; WILD-TYPE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
M. Kotler et al., "HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) PROTEIN VIF INHIBITS THE ACTIVITY OF HIV-1 PROTEASE IN BACTERIA AND IN-VITRO", Journal of virology, 71(8), 1997, pp. 5774-5781

Abstract

Human immunodeficiency virus type 1 (HIV-1) Vif is required for productive infection of T lymphocytes and macrophages, Virions produced in the absence of Vif have abnormal core morphology and those produced inprimary T cells carry immature core proteins and low levels of maturecapsid (M. Simm, M. Shahabuddin, W. Chao. J. S. Allan, and D. J. Volskg, J. Virol, 69:3582-1586, 1995), To investigate whether Vif influences the activity of HIV-1 protease (PR), the viral enzyme which is responsible for processing Gag and Gag-Pol precursor polyproteins into mature virion components, we transformed bacteria to inducibly express truncated Gag-Pol fusion proteins and Vif, We examined the cleavage of polyproteins consisting of matrix to PR (Gag-PR), capsid to PR (CA-PR),and p6(Pol) to PR (p6(pol)-PR) and evaluated HIV-1 protein processingat specific sites by Western blotting using antibodies against matrix, capsid, and PR proteins, We found that Vif modulates HIV-1 PR activity in bacteria mainly by preventing the release of mature MA and CA from Gag-PR, CA from CA-PR, and p6(Pol) from p6(Pol)-PR, with other cleavages being less affected. Using subconstructs of Vif, we mapped this activity to the N-terminal half of the molecule. thus identifying a new functional domain of Vif. Kinetic study of p6(Pol)-PR autocatalysis in the presence or absence of Vif revealed that Vif and N'Vif reduce the rate of PR-mediated proteolysis of this substrate, In an assay of in vitro proteolysis of a synthetic peptide substrate by purified recombinant PR we found that recombinant Vif and the N-terminal half of themolecule specifically inhibit PR activity at a molar ratio of the N-terminal half of Vif to PR of about 1, These results suggest a mechanism and site of action of Vif in HIV-1 replication and demonstrate novelregulation of a lentivirus PR by an autologous viral protein acting in trans.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:44:11