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Titolo:
Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain
Autore:
Sei, S; Yang, QE; ONeill, D; Yoshimura, K; Nagashima, K; Mitsuya, H;
Indirizzi:
NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, HIV Clin Interface Lab,Frederick, MD 21702 USA NCI Frederick MD USA 21702 HIV Clin Interface Lab,Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Cell & Mol Struct, Frederick, MD 21702 USA NCI Frederick MD USA 21702 Lab Cell & Mol Struct, Frederick, MD 21702 USA NCI, Expt Retrovirol Sect, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 I, Expt Retrovirol Sect, Bethesda, MD 20892 USA Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan Kumamoto Univ Kumamoto Japan 860 ept Internal Med 2, Kumamoto 860, Japan
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 10, volume: 74, anno: 2000,
pagine: 4621 - 4633
SICI:
0022-538X(200005)74:10<4621:IOAKTS>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PEPTIDE NUCLEIC-ACIDS; POLYMERASE CHAIN-REACTION; HIV PROTEASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; CHRONICALLY INFECTED-CELLS; SMALL-MOLECULE INHIBITOR; BLOOD MONONUCLEAR-CELLS; MAMMARY-TUMOR VIRUS; AUG INITIATOR CODON; CD4(+) T-CELLS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
154
Recensione:
Indirizzi per estratti:
Indirizzo: Sei, S NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, HIV Clin Interface Lab,Bldg 322,Rm 27B,POB B, Frederick, MD 21702 USA NCI Bldg 322,Rm 27B,POB B Frederick MD USA 21702 rick, MD 21702 USA
Citazione:
S. Sei et al., "Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain", J VIROLOGY, 74(10), 2000, pp. 4621-4633

Abstract

Although the full sequence of the human immunodeficiency virus type 1 (HIV-1) genome has been known for more than a decade, effective genetic antivirals have Set to be developed. Here we show that, of 22 regions examined, one highly conserved sequence (ACTCTTTGGCAACGA) near the 3' end of the HIV-1 gag-pol transframe region, encoding viral protease residues 4 to 8 and a C-terminal Vpr-binding motif of p6(Gag) protein in two different reading frames, can be successfully targeted by an antisense peptide nucleic acid oligomer named PNA(PR2). A disrupted translation of gag-pol mRNA induced at the PNA(PR2)-annealing site resulted in a decreased synthesis of pr160(Gag-Pol)polyprotein, hence the viral protease, a predominant expression of pr55(Gag) devoid of a fully functional p6(Gag) protein, and the excessive intracellular cleavage of Gag precursor proteins, hindering the processes of virionassembly. Treatment with PNA(PR2) abolished virion production by up to 99%in chronically HIV-l-infected H9 cells and in peripheral blood mononuclearcells infected with clinical HIV-1 isolates with the multidrug-resistant phenotype. This particular segment of the gag-pol transframe gene appears tooffer a distinctive advantage over other regions in invading viral structural genes and restraining HIV-1 replication in infected cells and may potentially be exploited as a novel antiviral genetic target.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/10/20 alle ore 05:57:16