H3N2 Canine, Mutant
Description
Origin and Evolutionary Trajectory
H3N2 CIV originated from avian influenza viruses (AIVs) in Asia, with the first isolation in dogs reported in South Korea in 2006 . Key evolutionary milestones include:
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2006–2012: Early clades (0–3) showed limited transmissibility and retained avian-like receptor binding (α–2,3-linked sialosides) .
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2012–2016: Clades 4–5 emerged, achieving 100% transmission efficiency in dogs and dual receptor binding (α–2,3 and α–2,6 sialosides) .
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2019–present: Clade 5.1 strains exhibit enhanced acid stability (activation pH 5.2) and human-like receptor affinity, enabling aerosol transmission in ferrets .
Phylogenetic analyses reveal sustained circulation in China, with repeated introductions into North America via dog imports .
Key Genetic Mutations Driving Adaptation
Adaptive mutations in H3N2 CIVs have been identified across multiple genes:
| Gene | Mutation | Functional Impact | Clade |
|---|---|---|---|
| HA | G146S | Shift to human-like α–2,6-linked sialoside recognition | Clade 4+ |
| HA | N188D | Increased HA acid stability (pH 5.2) and thermostability | Clade 5+ |
| PB1 | D154G | Enhanced polymerase activity, promoting replication in human cells | Clade 5+ |
| PB2 | G590S | Improved replication in mammalian cells | Clade E2 |
| NS1 | 13-aa deletion | Increased virulence in mice | Clade E |
These mutations mirror those found in human-adapted H3N2 strains, suggesting convergent evolution .
Clinical Impact on Canine Hosts
Experimental infections in dogs reveal escalating pathogenicity:
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Symptoms: Fever, nasal discharge, coughing, pneumonia, and extrapulmonary spread to liver, spleen, and brain .
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Viral Shedding: Detected in respiratory and digestive tracts, with peak transmission 4–6 days post-infection .
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Pathology: Lung consolidation, hepatization, and diffuse congestion observed in autopsies .
Later clades (e.g., clade 5.1) shorten transmission intervals and increase replication efficiency in dogs by 40% compared to early strains .
Zoonotic Potential and Public Health Risks
H3N2 CIVs have acquired traits that heighten spillover risks:
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Receptor Binding: Clade 5+ viruses bind human SAα2,6Gal receptors .
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Aerosol Transmission: 100% transmission rate in ferrets, a model for human spread .
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Human Susceptibility: Serological studies show minimal preexisting immunity in human populations .
Notably, PB2-107N and HA-G16S mutations in recent Chinese isolates (2022–2024) mirror substitutions in human H3N2 viruses, further bridging host compatibility .
Global Epidemiology and Antigenic Drift
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Asia: Enzootic in China and South Korea, with clades D, E1, and E2 circulating since 2014 .
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North America: Introduced via clades D and E1 (2015–2017), followed by post-2020 reintroductions from China .
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Antigenic Evolution: Seven antigenic groups (A–G) have emerged, driven by HA head domain mutations (e.g., V128I, A289S) .
Surveillance and Mitigation Strategies
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Monitoring: Active genomic surveillance in dogs and cats is critical, as feline-adapted strains (e.g., HA1-K299R) show increased thermal resistance and pH stability .
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Vaccines: Current vaccines target clades 0–3; updates are needed for clade 5.1 antigens .
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One Health Approach: Prioritize limiting intercontinental dog transport to reduce viral spread .
Product Specs
E. coli.
Product Science Overview
Hemagglutinin (HA) is a glycoprotein found on the surface of the influenza viruses, playing a crucial role in the virus’s ability to infect host cells. The H3N2 subtype of the Influenza A virus has been a significant concern due to its ability to infect multiple species, including humans, birds, and dogs. The recombinant, mutant form of H3N2 canine influenza virus (CIV) has garnered attention due to its unique properties and implications for public health.
Hemagglutinin is responsible for binding the virus to the host cell receptors, facilitating viral entry. It consists of two subunits: HA1 and HA2. The HA1 subunit contains the receptor-binding site, while the HA2 subunit is involved in the fusion of the viral and host cell membranes. Mutations in the HA protein can significantly alter the virus’s infectivity and antigenicity .
The H3N2 CIV was first identified in South Korea in 2007 and has since spread to other regions, including the United States. This virus is believed to have originated from avian influenza viruses and adapted to infect dogs. The H3N2 CIV poses a threat to public health due to its potential for cross-species transmission .
Recombinant H3N2 viruses are engineered to study the effects of specific mutations on the virus’s properties. These mutations can affect the virus’s ability to bind to host receptors, its thermal stability, and its antigenic properties. For example, the V223I substitution in the HA protein has been shown to reduce the virus’s binding affinity to human-type receptors while enhancing its thermal stability .
The recombinant, mutant forms of H3N2 CIV are valuable tools for understanding the virus’s behavior and developing effective vaccines. Studies have shown that current human H3N2 vaccines do not confer protection against H3N2 CIVs, highlighting the need for continuous surveillance and vaccine development .
