Reduced levels of neuraminidase of influenza A viruses correlate with attenuated phenotypes in mice

Alicia Solorzano, Hongyong Zheng, Ervin Fodor, George G. Brownlee, Peter Palese, Adolfo García-Sastre

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


We have previously obtained four transfectant influenza A viruses containing neuraminidase (NA) genes with mutated base pairs in the conserved double-stranded RNA region of the viral promoter by using a ribonucleoprotein transfection system. Two mutant viruses (D2 and D1/2) which share a C-G→A-U mutation at positions 11 and 12 of the 3' and 5' ends, respectively, of the NA gene, showed an approximate 10-fold reduction of NA-specific mRNA and protein levels. These viruses have now allowed us to determine the effects of decreased NA levels on virus pathogenicity. Both D2 and D1/2 viruses were highly attenuated in mice, and their replication in mouse lungs was highly compromised as compared with wild-type influenza A/WSN/33 virus. The results highlight the importance of the level of NA activity in the biological cycle and virulence of influenza viruses. Importantly, mice immunized by a single intranasal administration of 103 infectious units of D2 or D1/2 viruses were protected against challenge with a lethal dose of wild-type influenza virus. Attenuation of influenza viruses by mutations resulting in the decreased expression of a viral protein represents a novel strategy which could be considered for the generation of live attenuated influenza virus vaccines.

Original languageEnglish
Pages (from-to)737-742
Number of pages6
JournalJournal of General Virology
Issue number3
StatePublished - 2000


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