Host-range shift of H3N8 canine influenza virus: a phylodynamic analysis of its origin and adaptation from equine to canine host

Abstract Prior to the emergence of H3N8 canine influenza virus (CIV) and the latest avian-origin H3N2 CIV, there was no evidence of a circulating canine-specific influenza virus. Molecular and epidemiological evidence suggest that H3N8 CIV emerged from H3N8 equine influenza virus (EIV). This host-range shift of EIV from equine to canine hosts and its subsequent establishment as an enzootic CIV is unique because this host-range shift was from one mammalian host to another. To further understand this host-range shift, we conducted a comprehensive phylodynamic analysis using all the available whole-genome sequences of H3N8 CIV. We found that (1) the emergence of H3N8 CIV from H3N8 EIV occurred in approximately 2002; (2) this interspecies transmission was by a reassortant virus of the circulating Florida-1 clade H3N8 EIV; (3) once in the canine species, H3N8 CIV spread efficiently and remained an enzootic virus; (4) H3N8 CIV evolved and diverged into multiple clades or sublineages, with intra and inter-lineage reassortment. Our results provide a framework to understand the molecular basis of host-range shifts of influenza viruses and that dogs are potential “mixing vessels” for the establishment of novel influenza viruses.

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Host Adaptive Evolution of Avian-Origin H3N2 Canine Influenza Virus

Frontiers in Microbiology ◽

10.3389/fmicb.2021.655228 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fucheng Guo ◽

Ayan Roy ◽

Ruichen Wang ◽

Jinjin Yang ◽

Zhipeng Zhang ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Evolutionary Process ◽

Cellular Systems ◽

Interspecies Transmission ◽

Mammalian Host ◽

Immune Recognition ◽

Canine Influenza Virus ◽

Avian Origin ◽

Canine Influenza

Since its first isolation in around 2007, the avian-origin H3N2 canine influenza virus (CIV) has become established and continues to circulate in dog populations. This virus serves as a useful model for deciphering the complex evolutionary process of interspecies transmission of influenza A virus (IAV) from one species to its subsequent circulation in another mammalian host. The present investigation is a comprehensive effort to identify and characterize genetic changes that accumulated in the avian-origin H3N2 CIV during its circulation in the dog. We revealed that H3N2 CIV experiences greater selection pressure with extremely high global non-synonymous to synonymous substitution ratios per codon (dN/dS ratio) for each gene compared to the avian reservoir viruses. A total of 54 amino acid substitutions were observed to have accumulated and become fixed in the H3N2 CIV population based on our comprehensive codon-based frequency diagram analysis. Of these substitutions, 11 sites also display high prevalence in H3N8 CIV, indicating that convergent evolution has occurred on different lineages of CIV. Notably, six substitutions, including HA-G146S, M1-V15I, NS1-E227K, PA-C241Y, PB2-K251R, and PB2-G590S, have been reported to play imperative roles in facilitating the transmission and spillover of IAVs across species barriers. Most of these substitutions were found to have become fixed in around 2015, which might have been a favorable factor that facilitating the spread of these CIV lineages from South Asia to North America and subsequent further circulation in these areas. We also detected 12 sites in six viral genes with evidence for positive selection by comparing the rates of non-synonymous and synonymous substitutions at each site. Besides, our study reports trends of enhanced ongoing adaptation of H3N2 CIV to their respective host cellular systems, based on the codon adaptation index analysis, which points toward increasing fitness for efficient viral replication. In addition, a reduction in the abundance of the CpG motif, as evident from an analysis of relative dinucleotide abundance, may contribute to the successful evasion of host immune recognition. The present study provides key insights into the adaptive changes that have accumulated in the avian-origin H3N2 viral genomes during its establishment and circulation into dog populations.

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A novel reassortant canine H3N1 influenza virus between pandemic H1N1 and canine H3N2 influenza viruses in Korea

Journal of General Virology ◽

10.1099/vir.0.037739-0 ◽

2012 ◽

Vol 93 (3) ◽

pp. 551-554 ◽

Cited By ~ 72

Author(s):

Daesub Song ◽

Hyoung-Joon Moon ◽

Dong-Jun An ◽

Hye-Young Jeoung ◽

Hyekwon Kim ◽

...

Keyword(s):

Influenza Virus ◽

Clinical Signs ◽

Influenza Viruses ◽

Influenza Surveillance ◽

Pandemic H1n1 ◽

The Novel ◽

Canine Influenza Virus ◽

Ha Gene ◽

Pandemic Influenza H1n1 ◽

Canine Influenza

During recent canine influenza surveillance in South Korea, a novel H3N1 canine influenza virus (CIV) that is a putative reassortant between pandemic H1N1 2009 and H3N2 CIVs was isolated. Genetic analysis of eight genes of the influenza virus revealed that the novel H3N1 isolate presented high similarities (99.1–99.9 %) to pandemic influenza H1N1, except for in the haemagglutinin (HA) gene. The HA gene nucleotide sequence of the novel CIV H3N1 was similar (99.6 %) to that of CIV H3N2 isolated in Korea and China. Dogs infected with the novel H3N1 CIV did not show any notable symptoms, in contrast to dogs infected with H3N2 CIV. Despite no visible clinical signs of disease, nasal shedding of virus was detected and the infected dogs presented mild histopathological changes.

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Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus

Journal of Virology ◽

10.1128/jvi.03395-14 ◽

2015 ◽

Vol 89 (10) ◽

pp. 5406-5418 ◽

Cited By ~ 38

Author(s):

Henan Zhu ◽

Joseph Hughes ◽

Pablo R. Murcia

Keyword(s):

Influenza Virus ◽

North American ◽

Influenza A ◽

Influenza Viruses ◽

Animal Origin ◽

Influenza A Viruses ◽

Canine Influenza Virus ◽

Zoonotic Infections ◽

Avian Origin ◽

Canine Influenza

ABSTRACTInfluenza A viruses (IAVs) are maintained mainly in wild birds, and despite frequent spillover infections of avian IAVs into mammals, only a small number of viruses have become established in mammalian hosts. A new H3N2 canine influenza virus (CIV) of avian origin emerged in Asia in the mid-2000s and is now circulating in dog populations of China and South Korea, and possibly in Thailand. The emergence of CIV provides new opportunities for zoonotic infections and interspecies transmission. We examined 14,764 complete IAV genomes together with all CIV genomes publicly available since its first isolation until 2013. We show that CIV may have originated as early as 1999 as a result of segment reassortment among Eurasian and North American avian IAV lineages. We also identified amino acid changes that might have played a role in CIV emergence, some of which have not been previously identified in other cross-species jumps. CIV evolves at a lower rate than H3N2 human influenza viruses do, and viral phylogenies exhibit geographical structure compatible with high levels of local transmission. We detected multiple intrasubtypic and heterosubtypic reassortment events, including the acquisition of the NS segment of an H5N1 avian influenza virus that had previously been overlooked. In sum, our results provide insight into the adaptive changes required by avian viruses to establish themselves in mammals and also highlight the potential role of dogs to act as intermediate hosts in which viruses with zoonotic and/or pandemic potential could originate, particularly with an estimated dog population of ∼700 million.IMPORTANCEInfluenza A viruses circulate in humans and animals. This multihost ecology has important implications, as past pandemics were caused by IAVs carrying gene segments of both human and animal origin. Adaptive evolution is central to cross-species jumps, and this is why understanding the evolutionary processes that shape influenza A virus genomes is key to elucidating the mechanisms underpinning viral emergence. An avian-origin canine influenza virus (CIV) has recently emerged in dogs and is spreading in Asia. We reconstructed the evolutionary history of CIV and show that it originated from both Eurasian and North American avian lineages. We also identified the mutations that might have been responsible for the cross-species jump. Finally, we provide evidence of multiple reassortment events between CIV and other influenza viruses (including an H5N1 avian virus). This is a cause for concern, as there is a large global dog population to which humans are highly exposed.

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Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

Journal of Virology ◽

10.1128/jvi.02211-16 ◽

2016 ◽

Vol 91 (4) ◽

Cited By ~ 8

Author(s):

Aitor Nogales ◽

Laura Rodriguez ◽

Caroline Chauché ◽

Kai Huang ◽

Emma C. Reilly ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Influenza Viruses ◽

Influenza Vaccines ◽

Respiratory Pathogen ◽

Temperature Sensitive ◽

Wild Type ◽

Canine Influenza Virus ◽

Canine Influenza ◽

Better Than

ABSTRACT Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. IMPORTANCE Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.

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Intrahost Evolutionary Dynamics of Canine Influenza Virus in Naïve and Partially Immune Dogs

Journal of Virology ◽

10.1128/jvi.02469-09 ◽

2010 ◽

Vol 84 (10) ◽

pp. 5329-5335 ◽

Cited By ~ 54

Author(s):

Karin Hoelzer ◽

Pablo R. Murcia ◽

Gregory J. Baillie ◽

James L. N. Wood ◽

Stephan M. Metzger ◽

...

Keyword(s):

Influenza Virus ◽

Host Range ◽

Time Course ◽

Evolutionary Dynamics ◽

Viral Evolution ◽

Sequence Diversity ◽

Canine Influenza Virus ◽

Rapid Generation ◽

Canine Influenza ◽

Patterns And Processes

ABSTRACT The patterns and dynamics of evolution in acutely infecting viruses within individual hosts are largely unknown. To this end, we investigated the intrahost variation of canine influenza virus (CIV) during the course of experimental infections in naïve and partially immune dogs and in naturally infected dogs. Tracing sequence diversity in the gene encoding domain 1 of the hemagglutinin (HA1) protein over the time course of infection provided information on the patterns and processes of intrahost viral evolution and revealed some of the effects of partial host immunity. Viral populations sampled on any given day were generally characterized by mean pairwise genetic diversities between 0.1 and 0.2% and by mutational spectra that changed considerably on different days. Some observed mutations may have affected antigenicity or host range, including reversions of CIV host-associated mutations. Patterns of sequence diversity differed between naïve and vaccinated dogs, with some presumably antigenic mutations transiently reaching high frequency in the latter. CIV populations are therefore characterized by the rapid generation and clearance of genetic diversity. Potentially advantageous mutations arise readily during the course of single infections and may give rise to antigenic escape or host range variants.

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Microevolution of Canine Influenza Virus in Shelters and Its Molecular Epidemiology in the United States

Journal of Virology ◽

10.1128/jvi.01350-10 ◽

2010 ◽

Vol 84 (24) ◽

pp. 12636-12645 ◽

Cited By ~ 38

Author(s):

Jessica J. Hayward ◽

Edward J. Dubovi ◽

Janet M. Scarlett ◽

Stephanie Janeczko ◽

Edward C. Holmes ◽

...

Keyword(s):

United States ◽

New York ◽

Influenza Virus ◽

Gene Segment ◽

The United States ◽

Large Animal ◽

Equine Influenza Virus ◽

Animal Shelters ◽

Canine Influenza Virus ◽

Canine Influenza

ABSTRACT Canine influenza virus (CIV) emerged around 2000 when an equine influenza virus (EIV) was transmitted to dogs in Florida. After 2003, the canine virus was carried by infected greyhounds to various parts of the United States and then became established in several large animal shelters, where it has continued to circulate. To better understand the evolution of CIV since its emergence, and particularly its microevolution in spatially restricted populations, we examined multiple gene segments of CIV from dogs resident in two large animal shelters in New York City during the period 2006 to 2009. In particular, we focused on viruses circulating in the two shelters in 2008 and 2009, which we found shared a common ancestor. While viruses in each shelter were generally monophyletic, we observed some gene flow between them. These shelter sequences were compared to earlier CIV isolates. The shelter viruses differed in 1 to 6 amino acids in each gene segment compared to viruses isolated in Florida between 2003 and 2005 and in Colorado in 2006 and 2008. A comparison of the sequences of equine and canine viruses revealed amino acid replacements that distinguished the viruses from the two hosts, but no clear evidence of positive selection indicative of host adaptation was detected, suggesting that any host range adaptation in CIV occurred early in the emergence of this virus or even before it transferred to dogs.

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Emergence and Characterization of a Novel Reassortant Canine Influenza Virus Isolated from Cats

Pathogens ◽

10.3390/pathogens10101320 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1320

Author(s):

Jin Zhao ◽

Wanting He ◽

Meng Lu ◽

Haijian He ◽

Alexander Lai

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Reassortant Virus ◽

Human Influenza Virus ◽

Canine Influenza Virus ◽

Stray Cats ◽

Wide Range ◽

Canine Influenza

Cats are susceptible to a wide range of influenza A viruses (IAV). Furthermore, cats can serve as an intermediate host, and transfer avian influenza virus (AIV) H7N2 to a veterinarian. In this report, a novel reassortant influenza virus, designated A/feline/Jiangsu/HWT/2017 (H3N2), and abbreviated as FIV-HWT-2017, was isolated from nasal swab of a symptomatic cat in Jiangsu province, China. Sequence analysis indicated that, whilst the other seven genes were most similar to the avian-origin canine influenza viruses (CIV H3N2) isolated in China, the NS gene was more closely related to the circulating human influenza virus (H3N2) in the region. Therefore, FIV-HWT-2017 is a reassortant virus. In addition, some mutations were identified, and they were similar to a distinctive CIV H3N2 clade. Whether these cats were infected with the reassortant virus was unknown, however, this random isolation of a reassortant virus indicated that domestic or stray cats were “mixing vessel” for IAV cannot be ruled out. An enhanced surveillance for novel influenza virus should include pet and stray cats.

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