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Titolo:
GENETIC-VARIATION IN A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 LIVE-VIRUSMACACA-NEMESTRINA VACCINE MODEL
Autore:
RADAELLI A; KRAUS G; SCHMIDT A; BADEL P; MCCLURE J; HU SL; MORTON W; MORGHEN CD; WONGSTAAL F; LOONEY D;
Indirizzi:
VA MED CTR SAN DIEGO,3350 LA JOLLA VILLAGE DR SAN DIEGO CA 92161 UNIV CALIF SAN DIEGO,DEPT MED LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT BIOL LA JOLLA CA 92093 VA SAN DIEGO HEALTHCARE SYST SAN DIEGO CA 00000 UNIV MILAN,INST PHARMACOL SCI,DEPT PHARMACOL MILAN ITALY CNR CELLULAR & MOL PHARMACOL CTR MILAN ITALY UNIV WASHINGTON,REG PRIMATE RES CTR,CTR HLTH SCI SEATTLE WA 98195 BRISTOL MYERS SQUIBB,DIV RES SEATTLE WA 00000
Titolo Testata:
Journal of virology
fascicolo: 10, volume: 72, anno: 1998,
pagine: 7871 - 7884
SICI:
0022-538X(1998)72:10<7871:GIAHTL>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DISEASE PROGRESSION; EXPERIMENTAL-INFECTION; ENVELOPE GLYCOPROTEIN; BIOLOGICAL PHENOTYPE; RHESUS MACAQUES; VIRAL PHENOTYPE; HIV-2 ISOLATE; ENV GENE; EVOLUTION; SEQUENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
A. Radaelli et al., "GENETIC-VARIATION IN A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 LIVE-VIRUSMACACA-NEMESTRINA VACCINE MODEL", Journal of virology, 72(10), 1998, pp. 7871-7884

Abstract

Four pigtailed macaques were inoculated with an infectious, apathogenic human immunodeficiency virus type 2 (HIV-2) molecular clone (HIV-2,) and subsequently challenged with a highly pathogenic strain, HIV-2(287), together with two naive control animals. After challenge, two animals inoculated,vith a high dose of the immunizing strain were protected from CD4 decline and immunodeficiency. To examine the role of genetic heterogeneity in protection, fragments of the env gene were amplified from peripheral blood mononuclear cell DNA and plasma RNA of challenged animals by PCR, examined by using a heteroduplex tracking assay (HTA), and sequenced. By HTA, variation was detected principally withinthe V1 and V2 regions of envelope. Extent of variation in viral DNA clones as assessed by HTA correlated with inoculum size, as did the degree of variation in sequences of clones derived from viral DNA. Conversely, a rapid reduction in the number of plasma viral RNA variants wasnoted by HTA at 8 weeks postinfection in protected animals; this reduction was not present in naive or unprotected macaques. Sequences derived from plasma viral RNA were found to be more closely related than corresponding viral DNA sequences, and protection correlated with a significant reduction in variation in plasma RNA sequences in animals given the identical inocula of HIV-2(287). Nonsynonymous mutations were significantly less prevalent in the protected animals. An additional potential glycosylation site was predicted to be present in the V2 region in all but one clone, and amino acid signatures related to protection were identified in viral DNA and RNA clones within both the V1 and V2 regions. Examination of the role of viral variation in this HIV-2 live-virus vaccine model may provide valuable insights into immunopathogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 07:54:50