Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses
Open Access
- 7 February 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 9 (2), e1003176
- https://doi.org/10.1371/journal.ppat.1003176
Abstract
Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus. Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses. No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays. Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact. Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites. These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution. Influenza C viruses infect most humans during childhood. Unlike influenza A viruses, influenza C viruses exhibit little genetic variability and evolve at a comparably slower rate. Influenza A viruses exist as multiple subtypes and cause disease in numerous mammals. In contrast, influenza C viruses are comprised of a single subtype in its primary human host. Here we characterize a novel swine influenza virus, C/swine/Oklahoma/1334/2011 (C/OK), having only modest genetic similarity to human influenza C viruses. No cross-reaction was observed between C/OK and human influenza C viruses. Antibodies that cross react with C/OK were identified in a significant number of swine but not human sera samples, suggesting that C/OK circulates in pigs. Additionally, we show that C/OK is capable of infecting and transmitting by direct contact in both pigs and ferrets. These results suggest that C/OK represents a new subtype of influenza C viruses. This is significant, as co-circulation of multiple subtypes of influenza allows for rapid viral evolution through antigenic shift, a property previously only shown for influenza A viruses. The ability of C/OK to infect ferrets along with the absence of antibodies to C/OK in humans, suggests that such viruses may become a potential threat to human health.Keywords
This publication has 54 references indexed in Scilit:
- A distinct lineage of influenza A virus from batsProceedings of the National Academy of Sciences of the United States of America, 2012
- MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony MethodsMolecular Biology and Evolution, 2011
- Inactivated Seasonal Influenza Vaccines Increase Serum Antibodies to the Neuraminidase of Pandemic Influenza A(H1N1) 2009 Virus in an Age‐Dependent MannerThe Journal of Infectious Diseases, 2010
- Protein annotation and modelling servers at University College LondonNucleic Acids Research, 2010
- Rewiring the RNAs of influenza virus to prevent reassortmentProceedings of the National Academy of Sciences of the United States of America, 2009
- Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and MiceScience, 2009
- Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolutionProceedings of the National Academy of Sciences of the United States of America, 2008
- Structural basis for receptor specificity of influenza B virus hemagglutininProceedings of the National Academy of Sciences of the United States of America, 2007
- MUSCLE: multiple sequence alignment with high accuracy and high throughputNucleic Acids Research, 2004
- Electrostatics of nanosystems: Application to microtubules and the ribosomeProceedings of the National Academy of Sciences of the United States of America, 2001