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Titolo:
Pathogenic determinants of the mucosally transmissible CXCR4-specific SHIVSF33A2 map to env region
Autore:
Harouse, JM; Gettie, A; Tan, RCH; Eshetu, T; Ratterree, M; Blanchard, J; Cheng-Mayer, C;
Indirizzi:
Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA Rockefeller Univ New York NY USA 10016 DS Res Ctr, New York, NY 10016 USA Tulane Univ, Med Ctr, Tulane Reg Primate Res Ctr, Covington, LA USA TulaneUniv Covington LA USA lane Reg Primate Res Ctr, Covington, LA USA
Titolo Testata:
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
fascicolo: 3, volume: 27, anno: 2001,
pagine: 222 - 228
SICI:
1525-4135(20010701)27:3<222:PDOTMT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-TISSUE; T-CELL DEPLETION; RHESUS MACAQUES; VIRAL REPLICATION; IN-VIVO; ENVELOPE GLYCOPROTEINS; PERSISTENT INFECTION; SIV INFECTION; HIV-1;
Keywords:
animal disease model; AIDS; receptors, CXCR4; viral pathogenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Harouse, JM Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 455 1st Ave, NewYork, NY 10016 USA Rockefeller Univ 455 1st Ave New York NY USA 10016 Y 10016 USA
Citazione:
J.M. Harouse et al., "Pathogenic determinants of the mucosally transmissible CXCR4-specific SHIVSF33A2 map to env region", J ACQ IMM D, 27(3), 2001, pp. 222-228

Abstract

Infection of rhesus macaques with chimeric simian-human immunodeficiency viruses (SHIV) is an established method to study AIDS pathogenesis and is increasingly used to assess the efficacy of vaccine and antiviral candidates. For these reasons, a detailed understanding of those molecular determinants, which confer pathogenic potential to SHIV viruses, should assist in bothrational experimental design and interpretation of results. In this report, we describe the development and in vivo characterization of a pathogenic molecular clone, SHIVSF33A2, which contains an envelope sequence derived from the CXCR4-dependent isolate, HIV-I-SF33. Proviral DNA, amplified from a rhesus macaque infected with the pathogenic isolate SHIVSF33A, was substituted into the corresponding region of the parental, nonpathogenic SHIVSF33 genome creating the molecular clone SHIVSF33A2. Coreceptor specificity of SHIVSF33A2 was determined to be CXCR4 specific. Naive rhesus macaques were productively infected after a single exposure to cell-free SHIVSF33A2 by either the intravenous (IV) or intravaginal (IVAG) routes. Animals infected with SHIVSF33A2 suffered a severe loss of peripheral CD4(+) T cells and high acute plasma viremia with development of simian AIDS 9 months after inoculation. Sequence analysis identified 25 discreet amino acid changes within theV1-V5 regions of the envelope protein when compared with the nonpathogenicparental virus. These data indicate that domains within the HIV-I envelopeprotein are sufficient to define pathogenic potential in the context of the SIVmac239 genome.

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Documento generato il 26/01/20 alle ore 00:35:59