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Temperature sensitive mutants of influenza virus

Identifieur interne : 002B70 ( Main/Exploration ); précédent : 002B69; suivant : 002B71

Temperature sensitive mutants of influenza virus

Auteurs : Douglas D. Richman [États-Unis] ; Brian R. Murphy [États-Unis] ; Susan B. Spring [États-Unis] ; Marion T. Coleman [États-Unis] ; Robert M. Chanock [États-Unis]

Source :

RBID : ISTEX:C17192413A85EF1B5FFDB1BEEFBF1B0EB97CFB2B

English descriptors

Abstract

Abstract: The temperature-sensitive (ts) mutant recombinant influenza A/Hong Kong/1968-ts-1[E] (H3N2) previously was shown to possess properties desirable for a live attenuated vaccine. We investigated the regularity of transfer of these desirable properties by recombination to a newly emerged wild-type influenza A (H3N2) variant, A/Udorn/307/1972. Examination of Udorn/72-ts-1[E] recombinant clones confirmed that the ts-1[E] donor contained two independently segregating ts lesions, each of which segregated independently of the hemagglutinin and neuraminidase genes. Transfer of both of these ts lesions to a new recombinant was associated with a specific shutoff temperature in vitro of 38°, a moderate restriction of growth in the respiratory tract of hamsters, and infrequent reversion to ts+ phenotype in vivo. The absence of one of the two ts lesions in a Udorn/72-ts-1[E] recombinant clone resulted in a higher in vitro shutoff temperature (39°), less growth restriction in hamsters, and less genetic stability with regard to reversion to the ts+ phenotype. These results supported the hypothesis that well-defined ts lesions can be utilized as specific markers of attenuation which can be transferred to new, potentially epidemic, antigenic variants of influenza A virus.

Url:
DOI: 10.1016/0042-6822(75)90227-5


Affiliations:


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Le document en format XML

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<div type="abstract" xml:lang="en">Abstract: The temperature-sensitive (ts) mutant recombinant influenza A/Hong Kong/1968-ts-1[E] (H3N2) previously was shown to possess properties desirable for a live attenuated vaccine. We investigated the regularity of transfer of these desirable properties by recombination to a newly emerged wild-type influenza A (H3N2) variant, A/Udorn/307/1972. Examination of Udorn/72-ts-1[E] recombinant clones confirmed that the ts-1[E] donor contained two independently segregating ts lesions, each of which segregated independently of the hemagglutinin and neuraminidase genes. Transfer of both of these ts lesions to a new recombinant was associated with a specific shutoff temperature in vitro of 38°, a moderate restriction of growth in the respiratory tract of hamsters, and infrequent reversion to ts+ phenotype in vivo. The absence of one of the two ts lesions in a Udorn/72-ts-1[E] recombinant clone resulted in a higher in vitro shutoff temperature (39°), less growth restriction in hamsters, and less genetic stability with regard to reversion to the ts+ phenotype. These results supported the hypothesis that well-defined ts lesions can be utilized as specific markers of attenuation which can be transferred to new, potentially epidemic, antigenic variants of influenza A virus.</div>
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