Saturday, July 19, 2014

H3N8 structure determined – canine influenza originated in horses

Canine influenza is a highly contagious respiratory infection of dogs caused by a novel influenza virus (H3N8) that was first discovered in 2004. Like influenza in other species, the canine influenza virus causes a cough, sneezing and nasal discharge. A fever may also occur, but it is usually transient and rarely noticed by dog owners. H3N8 cannot be distinguish from other respiratory infections without diagnostic tests.

All dogs exposed to H3N8 become infected; about 80% become ill, the other 20% show no symptoms. Recovery time is about two weeks but some dogs progress to pneumonia, which is usually due to secondary bacterial infections. While the mortality rate for canine influenza is very low, the secondary pneumonia can be life-threatening in some cases. Canine influenza is an emergent disease in dogs.

Collins et al. (2014) recently used x-ray crystallography to determine the structure of the H3 hemagglutinins (HAs) in two different equine viruses and the canine virus. They found all three are very similar in structure with the majority of amino acid sequence differences between the two equine HAs located on the virus membrane. HAs of canine viruses are distinct in containing the amino acid substitution Trp-222→Leu in the receptor binding site that influences specificity for the receptor. In the canine and recent equine virus HAs a unique difference is observed by comparison with all other HAs examined to date. Analyses of site-specific mutant HAs indicate that a single amino acid substitution, Thr-30→Ser, influences interactions between N-terminal and C-terminal regions of the subdomain that are important in the structural changes required for membrane fusion activity. Both structural modifications may have facilitated the transmission of H3N8 influenza from horses to dogs.

The authors summarized the situation as follows. Equine influenza viruses of the H3N8 subtype were first isolated in 1963 from race horses in Miami. Since then they have caused numerous outbreaks of infection in horses around the world with serious disease and economic consequences. In 2004, again in Florida, an H3N8 virus was isolated from an outbreak of canine influenza and similar viruses have since been isolated from dogs in the United States and in Europe. Genetic comparisons indicate that the canine viruses are closely related to equine viruses that were in circulation in horses around 2000. In studies of differences in equine viruses isolated since 1963 and between equine and canine viruses, the sequences of genes for the hemagglutinin membrane glycoprotein (HA) have been compared. Sequence data for equine virus HAs indicate the evolution of four distinct lineages. The first was associated with antigenic drift, between 1963 and 1980, and following this three separate branches formed a “Eurasian” lineage, an “American” lineage, and a divided lineage containing two clades, “Florida” clade 1 and Florida clade 2. The HAs of the canine viruses are most similar to those of Florida clade 1 equines. The majority of amino acid sequence changes revealed from the analyses are in the HA1 component of HA, some in regions known to be antigenically important in H3 HAs, and several near the receptor binding site.

The pdf is available on-line.

Citation
Collins, P. J.,  et al. (2014). Recent evolution of equine influenza and the origin of canine influenza. Proceedings of the National Academy of Sciences, 201406606.

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