Balanced Hemagglutinin and Neuraminidase Activities Are Critical for Efficient Replication of Influenza A Virus

Author:

Mitnaul Lyndon J.1,Matrosovich Mikhail N.12,Castrucci Maria R.3,Tuzikov Alexander B.4,Bovin Nikolai V.4,Kobasa Darwyn1,Kawaoka Yoshihiro56

Affiliation:

1. Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 381011;

2. M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142782 Moscow,2 and

3. Dipartimento di Virologia, Istituto Superiore di Sanita, 00161 Rome, Italy3;

4. Shemyakin Institute of Bioorganic Chemistry, Miklukho-Maklaya, 117871 Moscow,4 Russia;

5. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, Wisconsin 537065; and

6. Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan6

Abstract

ABSTRACT The SD0 mutant of influenza virus A/WSN/33 (WSN), characterized by a 24-amino-acid deletion in the neuraminidase (NA) stalk, does not grow in embryonated chicken eggs because of defective NA function. Continuous passage of SD0 in eggs yielded 10 independent clones that replicated efficiently. Characterization of these egg-adapted viruses showed that five of the viruses contained insertions in the NA gene from the PB1, PB2, or NP gene, in the region linking the transmembrane and catalytic head domains, demonstrating that recombination of influenza viral RNA segments occurs relatively frequently. The other five viruses did not contain insertions in this region but displayed decreased binding affinity toward sialylglycoconjugates, compared with the binding properties of the parental virus. Sequence analysis of one of the latter viruses revealed mutations in the hemagglutinin (HA) gene, at sites in close proximity to the sialic acid receptor-binding pocket. These mutations appear to compensate for reduced NA function due to stalk deletions. Thus, balanced HA-NA functions are necessary for efficient influenza virus replication.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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