Effect of gene constellation and postreassortment amino acid change on the phenotypic features of H5 influenza virus reassortants.
Arch Virol. 2007; 152(6):1139-45.AV

Abstract

Reassortants between a low-pathogenic avian influenza virus strain A/Duck/Primorie/2621/2001 (H5N2) and a high-yield human influenza virus strain A/Puerto Rico/8/34 (H1N1) were generated, genotyped and analyzed with respect to their yield in embryonated chicken eggs, pathogenicity for mice, and immunogenicity. A reassortant having HA and NA genes from A/Duck/Primorie/2621/2001 virus and 6 genes from A/Puerto Rico/8/34 virus (6:2 reassortant) replicated efficiently in embryonated chicken eggs, the yields being intermediate between the yields of the avian parent virus and those of the A/Puerto Rico/8/34 parent strain. The reassortant having the HA gene from A/Duck/Primorie/2621/2001 virus and 7 genes from A/Puerto Rico/8/34 virus (7:1 reassortant) produced low yields. A variant of the 7:1 reassortant selected by serial passages in eggs had an amino acid substitution in the hemagglutinin (N244D, H3 numbering). The variant produced yields similar to those of the 6:2 reassortant. A 5:3 reassortant generated by a back-cross of the 6:2 reassortant with the avian parent and having PB1, HA and NA genes of A/Duck/Primorie/2621/2001 virus produced higher yields than the 7:1 or 6:2 reassortants, although still lower than the yields of A/Puerto Rico/8/34 virus. The 7:1, 6:2 and 5:3 reassortants were pathogenic for mice, with the level of virulence close to A/Puerto Rico/8/34 virus, in contrast to the extremely low pathogenicity of the A/Duck/Primorie/2621/2001 parent strain. Immunization of mice with an inactivated 6:2 H5N2 reassortant provided efficient immune protection against a reassortant virus containing the HA and NA genes of a recent H5N1 isolate. The results are discussed in connection with the problem of the improvement of vaccine strains against the threatening H5N1 pandemic.

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Authors+Show Affiliations

Rudneva IA
The D. I. Ivanovsky Institute of Virology RAMS, Moscow, Russia.
Timofeeva TA
No affiliation info available
Shilov AA
No affiliation info available
Kochergin-Nikitsky KS
No affiliation info available
Varich NL
No affiliation info available
Ilyushina NA
No affiliation info available
Gambaryan AS
No affiliation info available
Krylov PS
No affiliation info available
Kaverin NV
No affiliation info available

MeSH

Amino Acid SequenceAnimalsChick EmbryoFemaleGenes, ViralHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H5N1 SubtypeInfluenza A Virus, H5N2 SubtypeMicePhenotypeReassortant VirusesRecombination, GeneticVirulence

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17294090