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Titolo:
TEMPERATURE-SENSITIVE MUTANTS OF INFLUENZA-A VIRUS GENERATED BY REVERSE GENETICS AND CLUSTERED CHARGED TO ALANINE MUTAGENESIS
Autore:
PARKIN NT; CHIU P; COELINGH KL;
Indirizzi:
AVIRON,297 N BERNARDO AVE MT VIEW CA 94043
Titolo Testata:
Virus research
fascicolo: 1-2, volume: 46, anno: 1996,
pagine: 31 - 44
SICI:
0168-1702(1996)46:1-2<31:TMOIVG>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYSTEMATIC MUTATIONAL ANALYSIS; POLYMERASE BASIC PROTEIN-2; A VIRUS; RNA-POLYMERASE; P PROTEINS; PB2 GENE; COMPLEX; ATTENUATION; VACCINES; IDENTIFICATION;
Keywords:
INFLUENZA; PB2; TEMPERATURE SENSITIVE; ALANINE MUTAGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
N.T. Parkin et al., "TEMPERATURE-SENSITIVE MUTANTS OF INFLUENZA-A VIRUS GENERATED BY REVERSE GENETICS AND CLUSTERED CHARGED TO ALANINE MUTAGENESIS", Virus research, 46(1-2), 1996, pp. 31-44

Abstract

Temperature sensitive (ts) mutants of influenza A virus have the potential to serve as live attenuated (att) Virus vaccines. Previously, tsmutants were isolated by chemical mutagenesis or arose spontaneously,and most likely contained point mutations in one or more genes. Whilesufficiently attenuated, even the most genetically stable of these viruses was found to revert to a more virulent form in a seronegative vaccinee. Recently developed technology, however, allows the introduction of engineered mutations into the genome of influenza A and B viruses, permitting the rational design of attenuated mutants with the potential for increased genetic stability. To accomplish this goal, we have introduced ts mutations into the PB2 gene of A/Los Angeles/2/87 (H3N2)and rescued the mutated genes into infectious viruses. We have used clustered charged to alanine mutagenesis (substitution of alanine for charged amino acid residues which are present in clusters) of the PB2 gene to generate novel ts mutants. Viruses containing such ts PB2 geneswere attenuated in mice and ferrets. This approach has thus yielded several vaccine candidates with ts and attenuated characteristics in animal models. Combination of these mutations with each other or with other ts mutations may lead to a high level of genetic stability. Copyright (C) 1996 Elsevier Science B.V.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/10/20 alle ore 04:57:23