Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus
- PMID: 8411368
- PMCID: PMC238105
- DOI: 10.1128/JVI.67.11.6667-6673.1993
Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus
Abstract
The neuraminidase (NA) gene of influenza A/WSN/33 (WSN) virus has previously been shown to be associated with neurovirulence in mice and growth in Madin-Darby bovine kidney (MDBK) cells. Nucleotide sequence analysis has indicated that the NA of WSN virus lacks a conserved glycosylation site at position 130 (corresponding to position 146 in the N2 subtype). To investigate the role of this carbohydrate in viral pathogenicity, we used reverse genetics methods to generate a Glyc+ mutant virus, in which the glycosylation site Asn-130 was introduced into the WSN virus NA. Unlike the wild-type WSN virus, the Glyc+ mutant virus did not undergo multicycle replication in MDBK cells in the absence of trypsin, presumably because of lack of cleavage activation of infectivity. In contrast, revertant viruses derived from the Glyc+ mutant were able to replicate in MDBK cells without exogenous protease. Nucleotide sequence analysis revealed that the NAs of the revertant viruses had lost the introduced glycosylation site. In contrast to wild-type and revertant viruses, the Glyc+ mutant virus was not able to multiply in mouse brain. These results suggest that the absence of a glycosylation site at position 130 of the NA plays a key role in the neurovirulence of WSN virus in mice.
Similar articles
-
Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus.J Virol. 2001 Oct;75(19):9297-301. doi: 10.1128/JVI.75.19.9297-9301.2001. J Virol. 2001. PMID: 11533192 Free PMC article.
-
Virulence factors of influenza A viruses: WSN virus neuraminidase required for plaque production in MDBK cells.J Virol. 1977 Oct;24(1):170-6. doi: 10.1128/JVI.24.1.170-176.1977. J Virol. 1977. PMID: 561860 Free PMC article.
-
Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication.J Virol. 2005 Sep;79(18):11705-15. doi: 10.1128/JVI.79.18.11705-11715.2005. J Virol. 2005. PMID: 16140748 Free PMC article.
-
[Novel function of plasminogen-binding activity of the NA determines the pathogenicity of influenza A virus].Uirusu. 2004 Jun;54(1):83-91. doi: 10.2222/jsv.54.83. Uirusu. 2004. PMID: 15449908 Review. Japanese.
-
Toll-like receptor 9 ligand D-type oligodeoxynucleotide D35 as a broad inhibitor for influenza A virus replication that is associated with suppression of neuraminidase activity.Antiviral Res. 2016 May;129:81-92. doi: 10.1016/j.antiviral.2016.02.012. Epub 2016 Feb 26. Antiviral Res. 2016. PMID: 26923882 Free PMC article.
Cited by
-
The origin and virulence of the 1918 "Spanish" influenza virus.Proc Am Philos Soc. 2006 Mar;150(1):86-112. Proc Am Philos Soc. 2006. PMID: 17526158 Free PMC article.
-
Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus.Philos Trans R Soc Lond B Biol Sci. 2001 Dec 29;356(1416):1829-39. doi: 10.1098/rstb.2001.1020. Philos Trans R Soc Lond B Biol Sci. 2001. PMID: 11779381 Free PMC article. Review.
-
Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype.J Virol. 2003 Nov;77(21):11616-24. doi: 10.1128/jvi.77.21.11616-11624.2003. J Virol. 2003. PMID: 14557647 Free PMC article.
-
Influenza Hemagglutinin and Neuraminidase: Yin⁻Yang Proteins Coevolving to Thwart Immunity.Viruses. 2019 Apr 16;11(4):346. doi: 10.3390/v11040346. Viruses. 2019. PMID: 31014029 Free PMC article. Review.
-
Progress in identifying virulence determinants of the 1918 H1N1 and the Southeast Asian H5N1 influenza A viruses.Antiviral Res. 2008 Sep;79(3):166-78. doi: 10.1016/j.antiviral.2008.04.006. Epub 2008 May 23. Antiviral Res. 2008. PMID: 18547656 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical