Bacterial Neuraminidase Rescues Influenza Virus Replication from Inhibition by a Neuraminidase Inhibitor
Open Access
- 18 September 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (9), e45371
- https://doi.org/10.1371/journal.pone.0045371
Abstract
Influenza virus neuraminidase (NA) cleaves terminal sialic acid residues on oligosaccharide chains that are receptors for virus binding, thus playing an important role in the release of virions from infected cells to promote the spread of cell-to-cell infection. In addition, NA plays a role at the initial stage of viral infection in the respiratory tract by degrading hemagglutination inhibitors in body fluid which competitively inhibit receptor binding of the virus. Current first line anti-influenza drugs are viral NA-specific inhibitors, which do not inhibit bacterial neuraminidases. Since neuraminidase producing bacteria have been isolated from oral and upper respiratory commensal bacterial flora, we posited that bacterial neuraminidases could decrease the antiviral effectiveness of NA inhibitor drugs in respiratory organs when viral NA is inhibited. Using in vitro models of infection, we aimed to clarify the effects of bacterial neuraminidases on influenza virus infection in the presence of the NA inhibitor drug zanamivir. We found that zanamivir reduced progeny virus yield to less than 2% of that in its absence, however the yield was restored almost entirely by the exogenous addition of bacterial neuraminidase from Streptococcus pneumoniae. Furthermore, cell-to-cell infection was severely inhibited by zanamivir but restored by the addition of bacterial neuraminidase. Next we examined the effects of bacterial neuraminidase on hemagglutination inhibition and infectivity neutralization activities of human saliva in the presence of zanamivir. We found that the drug enhanced both inhibitory activities of saliva, while the addition of bacterial neuraminidase diminished this enhancement. Altogether, our results showed that bacterial neuraminidases functioned as the predominant NA when viral NA was inhibited to promote the spread of infection and to inactivate the neutralization activity of saliva. We propose that neuraminidase from bacterial flora in patients may reduce the efficacy of NA inhibitor drugs during influenza virus infection. (295 words).Keywords
This publication has 36 references indexed in Scilit:
- Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfectionVirology Journal, 2011
- The essentiality of α‐2‐macroglobulin in human salivary innate immunity against new H1N1 swine origin influenza A virusProteomics, 2010
- Multiple components contribute to ability of saliva to inhibit influenza virusesOral Microbiology and Immunology, 2008
- Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza PreparednessThe Journal of Infectious Diseases, 2008
- Professional oral care reduces influenza infection in elderlyArchives of Gerontology and Geriatrics, 2006
- Metabolism of glycoprotein-derived sialic acid and N-acetylglucosamine by Streptococcus oralisMicrobiology, 1996
- Inhibition of transcriptase activity of influenza A virus in vitro by anti-haemagglutinin antibodiesVaccine, 1985
- Purification and Properties of Neuraminidase from Vibrio choleraeJournal of General Microbiology, 1961
- Neuraminidase: the specific enzyme of influenza virus and Vibrio choleraeBiochimica et Biophysica Acta, 1957
- Enzymic Action of Viruses and Bacterial Products on Human Red CellsNature, 1948