Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses

• Published in: PLoS pathogens Vol. 9; no. 2; p. e1003176
• Main Authors: Hause, Ben M., Ducatez, Mariette, Collin, Emily A., Ran, Zhiguang, Liu, Runxia, Sheng, Zizhang, Armien, Anibal, Kaplan, Bryan, Chakravarty, Suvobrata, Hoppe, Adam D., Webby, Richard J., Simonson, Randy R., Li, Feng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2013; Public Library of Science (PLoS)
• Subjects: Amino acids; Animal biology; Animals; Antibodies, Viral - blood; Antigens, Viral - immunology; Base Sequence; Binding sites; Biology; Cell culture; Cell Culture Techniques; Comparative analysis; Evolution; Experiments; Ferrets; Gammainfluenzavirus - genetics; Gammainfluenzavirus - immunology; Gammainfluenzavirus - isolation & purification; Gammainfluenzavirus - ultrastructure; Genome, Viral - genetics; Health aspects; Hemagglutination Inhibition Tests; Hemagglutinins, Viral - genetics; Hemagglutinins, Viral - metabolism; Hogs; Host Specificity; Host-parasite relationships; Human health and pathology; Humans; Influenza; Life Sciences; Male; Microbiology and Parasitology; Models, Molecular; Molecular Sequence Data; Oklahoma; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - transmission; Orthomyxoviridae Infections - virology; Pandemics; Phylogeny; Physiological aspects; Proteins; Santé publique et épidémiologie; Sequence Analysis, DNA; Structural analysis; Swine; Swine Diseases - immunology; Swine Diseases - transmission; Swine Diseases - virology; Viral Fusion Proteins - genetics; Viral Fusion Proteins - metabolism; Viruses; Oklahoma; United States; Genome, Viral; Humans; Oklahoma; Models, Molecular; Molecular Sequence Data; Host Specificity; Male; Swine Diseases; Phylogeny; Antibodies, Viral; Ferrets; Sequence Analysis, DNA; Hemagglutination Inhibition Tests; Influenzavirus C; Animals; Antigens, Viral; Swine; Base Sequence; Hemagglutinins, Viral; Orthomyxoviridae Infections; Cell Culture Techniques; Viral Fusion Proteins
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003176

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.