Dataset Information

Evolution of the hemagglutinin gene of H3N8 canine influenza virus in dogs.

ABSTRACT: With the widespread use of a recently developed canine influenza virus (CIV) H3N8 vaccine, continual molecular evaluation of circulating CIVs is necessary for monitoring antigenic drift. The aim of this project was to further describe the genetic evolution of CIV, as well as determine any genetic variation within potential antigenic regions that might result in antigenic drift. To this end, the hemagglutinin gene of 19 CIV isolates from dogs residing in Colorado, New York, and South Carolina humane shelters was sequenced and compared to CIV strains isolated during 2003-2012. Phylogenetic analysis suggests that CIV might be diverging into two geographically distinct lineages. Using a mixed-effects model for evolution and single likelihood ancestor counting methods, several amino acid sites were found to be undergoing selection pressure. Additionally, a total of six amino acid changes were observed in two possible antigenic sites for CIVs isolated from Colorado and New York humane shelters between 2009 and 2011. As CIV isolates might be diverging into geographically distinct lineages, further experiments are warranted to determine the extent of antigenic drift occurring within circulating CIV.

SUBMITTER: Pecoraro HL

PROVIDER: S-EPMC4232753 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Evolution of the hemagglutinin gene of H3N8 canine influenza virus in dogs.

Pecoraro Heidi L HL Bennett Susi S Spindel Miranda E ME Landolt Gabriele A GA

Virus genes 20140724 3

With the widespread use of a recently developed canine influenza virus (CIV) H3N8 vaccine, continual molecular evaluation of circulating CIVs is necessary for monitoring antigenic drift. The aim of this project was to further describe the genetic evolution of CIV, as well as determine any genetic variation within potential antigenic regions that might result in antigenic drift. To this end, the hemagglutinin gene of 19 CIV isolates from dogs residing in Colorado, New York, and South Carolina hum ...[more]

PMID: 25056577

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Project description:Equine-origin H3N8 and avian-origin H3N2 canine influenza viruses (CIVs) prevalent in dogs are thought to pose a public health threat arising from intimate contact between dogs and humans. However, our understanding of CIV virulence is still limited. Influenza A virus PA-X is a fusion protein encoded in part by a +1 frameshifted open reading frame (X-ORF) in segment 3. The X-ORF can be translated in full-length (61-amino-acid) or truncated (41-amino-acid) form. Genetic analysis indicated that the X-ORFs of equine H3N8 and avian H3N2 influenza viruses encoded 61 amino acids but were truncated after introduction into dogs. To determine the effect of PA-X truncation on the biological characteristics of CIVs, we constructed four recombinant viruses on H3N8 and H3N2 CIV backgrounds bearing truncated or full-length PA-Xs. We observed that truncation of PA-X increased growth of both H3N8 and H3N2 CIVs in MDCK cells and suppressed expression from cotransfected plasmids in MDCK cells. Furthermore, truncation of PA-X enhanced viral pathogenicity in dogs, as shown by aggravated clinical symptoms and histopathological changes, increased viral replication in the respiratory system, and prolonged virus shedding. Additionally, CIVs with truncated PA-Xs were transmitted more efficiently in dogs. Global gene expression profiling of the lungs of infected dogs revealed that differentially expressed genes were mainly associated with inﬂammatory responses, which might contribute to the pathogenicity of PA-X-truncated CIVs. Our findings revealed that truncation of PA-X might be important for the adaptation of influenza viruses to dogs.IMPORTANCE Epidemics of equine-origin H3N8 and avian-origin H3N2 influenza viruses in canine populations are examples of successful cross-species transmission of influenza A viruses. Genetic analysis showed that the PA-X genes of equine H3N8 or avian H3N2 influenza viruses were full-length, with X-ORFs encoding 61 amino acids; however, those of equine-origin H3N8 or avian-origin H3N2 CIVs were truncated, suggesting that PA-X truncation occurred after transmission to dogs. In this study, we extended the PA-X genes of H3N8 and H3N2 CIVs and compared the biological characteristics of CIVs bearing different lengths of PA-X. We demonstrated that for both H3N8 and H3N2 viruses, truncation of PA-X increased virus yields in MDCK cells and enhanced viral replication, pathogenicity, and transmission in dogs. These results might reflect enhanced suppression of host gene expression and upregulation of genes related to inflammatory responses. Collectively, our data partially explain the conservation of truncated PA-X in CIVs.

Dataset Information

Evolution of the hemagglutinin gene of H3N8 canine influenza virus in dogs.

Publications

Evolution of the hemagglutinin gene of H3N8 canine influenza virus in dogs.

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