Transmission of avian-origin canine influenza viruses A (H3N2) in cats

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.

Download Full-text

Genetic characterization of avian-origin H3N2 canine influenza viruses isolated from Guangdong during 2006–2012

Virus Genes ◽

10.1007/s11262-013-0893-3 ◽

2013 ◽

Vol 46 (3) ◽

pp. 558-562 ◽

Cited By ~ 15

Author(s):

Heng Wang ◽

Kun Jia ◽

Wenbao Qi ◽

Minze Zhang ◽

Long Sun ◽

...

Keyword(s):

Genetic Characterization ◽

Influenza Viruses ◽

Avian Origin ◽

Canine Influenza

Download Full-text

Complete Genome Sequence of an Avian-Origin H3N2 Canine Influenza A Virus Isolated in Farmed Dogs in Southern China

Journal of Virology ◽

10.1128/jvi.01601-12 ◽

2012 ◽

Vol 86 (18) ◽

pp. 10238-10238 ◽

Cited By ~ 15

Author(s):

Shuo Su ◽

Nan Cao ◽

Jidang Chen ◽

Furong Zhao ◽

Huatao Li ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Genomic Sequence ◽

Southern China ◽

Phylogenetic Analyses ◽

Influenza Viruses ◽

Interspecies Transmission ◽

Avian Origin ◽

Canine Influenza ◽

Canine Influenza A Virus

We report here the complete genomic sequence of an avian-origin H3N2 canine influenza A virus containing multiple mutations in farmed dogs in southern China. Phylogenetic analyses of the sequences of all eight viral RNA segments demonstrated that these are wholly avian influenza viruses of the Asia lineage. To our knowledge, this is the first report of interspecies transmission of an avian H3N2 influenza virus to domestic farm dogs under natural conditions in Southern China. The amino acid information provided herein suggests that continued study is required to determine if this virus could be established in the farm dog population and pose potential threats to public health.

Download Full-text

A Multiplex RT-PCR Assay for Detection and Differentiation of Avian-Origin Canine H3N2, Equine-Origin H3N8, Human-Origin H3N2, and H1N1/2009 Canine Influenza Viruses

PLoS ONE ◽

10.1371/journal.pone.0170374 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0170374 ◽

Cited By ~ 5

Author(s):

Chenxi Wang ◽

Qian Wang ◽

Junyi Hu ◽

Honglei Sun ◽

Juan Pu ◽

...

Keyword(s):

Influenza Viruses ◽

Human Origin ◽

Rt Pcr ◽

Pcr Assay ◽

Avian Origin ◽

Canine Influenza

Download Full-text

The K186E Amino Acid Substitution in the Canine Influenza Virus H3N8 NS1 Protein Restores Its Ability To Inhibit Host Gene Expression

Journal of Virology ◽

10.1128/jvi.00877-17 ◽

2017 ◽

Vol 91 (22) ◽

Cited By ~ 9

Author(s):

Aitor Nogales ◽

Caroline Chauché ◽

Marta L. DeDiego ◽

David J. Topham ◽

Colin R. Parrish ◽

...

Keyword(s):

Gene Expression ◽

Amino Acid ◽

Immune Responses ◽

Influenza Viruses ◽

Innate Immune ◽

Host Gene ◽

Innate Immune Responses ◽

Host Gene Expression ◽

Avian Origin ◽

Canine Influenza

ABSTRACT Canine influenza viruses (CIVs) are the causative agents of canine influenza, a contagious respiratory disease in dogs, and include the equine-origin H3N8 and the avian-origin H3N2 viruses. Influenza A virus (IAV) nonstructural protein 1 (NS1) is a virulence factor essential for counteracting the innate immune response. Here, we evaluated the ability of H3N8 CIV NS1 to inhibit host innate immune responses. We found that H3N8 CIV NS1 was able to efficiently counteract interferon (IFN) responses but was unable to block general gene expression in human or canine cells. Such ability was restored by a single amino acid substitution in position 186 (K186E) that resulted in NS1 binding to the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a cellular protein involved in pre-mRNA processing. We also examined the frequency distribution of K186 and E186 among H3N8 CIVs and equine influenza viruses (EIVs), the ancestors of H3N8 CIV, and experimentally determined the impact of amino acid 186 in the ability of different CIV and EIV NS1s to inhibit general gene expression. In all cases, the presence of E186 was responsible for the control of host gene expression. In contrast, the NS1 protein of H3N2 CIV harbors E186 and blocks general gene expression in canine cells. Altogether, our results confirm previous studies on the strain-dependent ability of NS1 to block general gene expression. Moreover, the observed polymorphism on amino acid 186 between H3N8 and H3N2 CIVs might be the result of adaptive changes acquired during long-term circulation of avian-origin IAVs in mammals. IMPORTANCE Canine influenza is a respiratory disease of dogs caused by two CIV subtypes, the H3N8 and H3N2 viruses, of equine and avian origins, respectively. Influenza NS1 is the main viral factor responsible for the control of host innate immune responses, and changes in NS1 can play an important role in host adaptation. Here we assessed the ability of H3N8 CIV NS1 to inhibit host innate immune responses and gene expression. The H3N8 CIV NS1 did not block host gene expression, but this activity was restored by a single amino acid substitution (K186E), which was responsible for NS1 binding to the host factor CPSF30. In contrast, the H3N2 CIV NS1, which contains E186, blocks general gene expression. Our results suggest that the ability to block host gene expression is not required for influenza virus replication in mammals but might be important in the long-term adaptation of avian-origin influenza viruses to mammals.

Download Full-text

Truncation of PA-X Contributes to Virulence and Transmission of H3N8 and H3N2 Canine Influenza Viruses in Dogs

Journal of Virology ◽

10.1128/jvi.00949-20 ◽

2020 ◽

Vol 94 (15) ◽

Author(s):

Litao Liu ◽

Shikai Song ◽

Ye Shen ◽

Chao Ma ◽

Tong Wang ◽

...

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Influenza A ◽

Inflammatory Responses ◽

Mdck Cells ◽

Influenza Viruses ◽

Full Length ◽

Avian Origin ◽

Canine Influenza ◽

H3n2 Influenza

ABSTRACT 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.

Download Full-text

Evolution and Adaptation of the Avian H7N9 Virus into the Human Host

Microorganisms ◽

10.3390/microorganisms8050778 ◽

2020 ◽

Vol 8 (5) ◽

pp. 778

Author(s):

Andrew T. Bisset ◽

Gerard F. Hoyne

Keyword(s):

Amino Acid ◽

Avian Influenza ◽

Influenza A ◽

Amino Acid Sequences ◽

Influenza Viruses ◽

Amino Acid Substitutions ◽

Upper Respiratory Tract ◽

Viral Polymerase ◽

Evolutionary Changes ◽

Avian Origin

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.

Download Full-text

Equine and canine influenza: a review of current events

Animal Health Research Reviews ◽

10.1017/s1466252310000046 ◽

2010 ◽

Vol 11 (1) ◽

pp. 43-51 ◽

Cited By ~ 28

Author(s):

E. Paul J. Gibbs ◽

Tara C. Anderson

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Influenza A ◽

One Health ◽

Control Strategies ◽

Close Association ◽

Companion Animals ◽

Emerging Diseases ◽

Influenza Viruses ◽

Canine Influenza

AbstractIn the past decade, the pandemics of highly pathogenic avian influenza H5N1 and the novel H1N1 influenza have both illustrated the potential of influenza viruses to rapidly emerge and spread widely in animals and people. Since both of these viruses are zoonotic, these pandemics have been the driving force behind a renewed commitment by the medical and veterinary professions to practice One World, One Health for the control of infectious diseases. The discovery in 2004 that an equine origin H3N8 influenza virus was the cause of an extensive epidemic of respiratory disease in dogs in the USA came as a surprise; at that time dogs were thought to be refractory to infection with influenza viruses. In 2007, a second emerging canine influenza was confirmed in Korea, but this time the causal virus was an H3N2 avian influenza virus. This review focuses on recent events associated with equine and canine influenza viruses. While these viruses do not appear to be zoonotic, the close association between humans and dogs, and to a lesser extent horses, demands that we develop better surveillance and control strategies for emerging diseases in companion animals within the context of One World, One Health.

Download Full-text