scholarly journals Host Adaptive Evolution of Avian-Origin H3N2 Canine Influenza Virus

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.

scholarly journals Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus

2015 ◽  
Vol 89 (10) ◽  
pp. 5406-5418 ◽  
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.

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

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Wanting He ◽  
Gairu Li ◽  
Ruyi Wang ◽  
Weifeng Shi ◽  
Kemang Li ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Host Range ◽  
Influenza Viruses ◽  
Range Shift ◽  
Interspecies Transmission ◽  
Mammalian Host ◽  
Equine Influenza Virus ◽  
Canine Influenza Virus ◽  
Canine Influenza ◽  
Phylodynamic Analysis

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.

scholarly journals In VitroSusceptibility of Canine Influenza A (H3N8) Virus to Nitazoxanide and Tizoxanide

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Laura V. Ashton ◽  
Robert L. Callan ◽  
Sangeeta Rao ◽  
Gabriele A. Landolt
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
The United States ◽  
Canine Influenza Virus ◽  
Valuable Adjunct ◽  
Canine Influenza ◽  
The Impact ◽  
H3n8 Virus

Infection of dogs with canine influenza virus (CIV) is considered widespread throughout the United States following the first isolation of CIV in 2004. While vaccination against influenza A infection is a common and important practice for disease control, antiviral therapy can serve as a valuable adjunct in controlling the impact of the disease. In this study, we examined the antiviral activity of nitazoxanide (NTZ) and tizoxanide (TIZ) against three CIV isolatesin vitro. NTZ and TIZ inhibited virus replication of all CIVs with 50% and 90% inhibitory concentrations ranging from 0.17 to 0.21 μMand from 0.60 to 0.76 μM, respectively. These results suggest that NTZ and TIZ are effective against CIV and may be useful for treatment of canine influenza in dogs but further investigation of thein vivoefficacy against CIV as well as the drug's potential for toxicity in dogs is needed.

Short communication: isolation and phylogenetic analysis of an avian-origin H3N2 canine influenza virus in dog shelter, China

Virus Genes ◽  
2013 ◽  
Vol 46 (3) ◽  
pp. 554-557 ◽  
Author(s):  
Shuo Su ◽  
Ziguo Yuan ◽  
Jidang Chen ◽  
Jiexiong Xie ◽  
Huatao Li ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Influenza Virus ◽  
Short Communication ◽  
Canine Influenza Virus ◽  
Avian Origin ◽  
Canine Influenza

scholarly journals Multiple Incursions and Recurrent Epidemic Fade-Out of H3N2 Canine Influenza A Virus in the United States

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Ian E. H. Voorhees ◽  
Benjamin D. Dalziel ◽  
Amy Glaser ◽  
Edward J. Dubovi ◽  
Pablo R. Murcia ◽  
...  
Keyword(s):  
United States ◽  
Influenza A ◽  
The United States ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Canine Influenza Virus ◽  
Emerging Virus ◽  
Avian Origin ◽  
Canine Influenza ◽  
Comprehensive Surveillance

ABSTRACT Avian-origin H3N2 canine influenza virus (CIV) transferred to dogs in Asia around 2005, becoming enzootic throughout China and South Korea before reaching the United States in early 2015. To understand the posttransfer evolution and epidemiology of this virus, particularly the cause of recent and ongoing increases in incidence in the United States, we performed an integrated analysis of whole-genome sequence data from 64 newly sequenced viruses and comprehensive surveillance data. This revealed that the circulation of H3N2 CIV within the United States is typified by recurrent epidemic burst–fade-out dynamics driven by multiple introductions of virus from Asia. Although all major viral lineages displayed similar rates of genomic sequence evolution, H3N2 CIV consistently exhibited proportionally more nonsynonymous substitutions per site than those in avian reservoir viruses, which is indicative of a large-scale change in selection pressures. Despite these genotypic differences, we found no evidence of adaptive evolution or increased viral transmission, with epidemiological models indicating a basic reproductive number, R0, of between 1 and 1.5 across nearly all U.S. outbreaks, consistent with maintained but heterogeneous circulation. We propose that CIV's mode of viral circulation may have resulted in evolutionary cul-de-sacs, in which there is little opportunity for the selection of the more transmissible H3N2 CIV phenotypes necessary to enable circulation through a general dog population characterized by widespread contact heterogeneity. CIV must therefore rely on metapopulations of high host density (such as animal shelters and kennels) within the greater dog population and reintroduction from other populations or face complete epidemic extinction. IMPORTANCE The relatively recent appearance of influenza A virus (IAV) epidemics in dogs expands our understanding of IAV host range and ecology, providing useful and relevant models for understanding critical factors involved in viral emergence. Here we integrate viral whole-genome sequence analysis and comprehensive surveillance data to examine the evolution of the emerging avian-origin H3N2 canine influenza virus (CIV), particularly the factors driving ongoing circulation and recent increases in incidence of the virus within the United States. Our results provide a detailed understanding of how H3N2 CIV achieves sustained circulation within the United States despite widespread host contact heterogeneity and recurrent epidemic fade-out. Moreover, our findings suggest that the types and intensities of selection pressures an emerging virus experiences are highly dependent on host population structure and ecology and may inhibit an emerging virus from acquiring sustained epidemic or pandemic circulation.

scholarly journals Complete Genome Sequence of an Avian-Origin H3N2 Canine Influenza Virus Isolated from Dogs in South Korea

2012 ◽  
Vol 86 (17) ◽  
pp. 9548-9549 ◽  
Author(s):  
S.-J. Park ◽  
H.-J. Moon ◽  
B.-K. Kang ◽  
M. Hong ◽  
W. Na ◽  
...  
Keyword(s):  
Influenza Virus ◽  
South Korea ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Canine Influenza Virus ◽  
Avian Origin ◽  
Canine Influenza

Avian-origin H3N2 canine influenza virus circulating in farmed dogs in Guangdong, China

2013 ◽  
Vol 19 ◽  
pp. 251-256 ◽  
Author(s):  
Shuo Su ◽  
Ye Chen ◽  
Fu-Rong Zhao ◽  
Ji-Dang Chen ◽  
Jie-Xiong Xie ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Canine Influenza Virus ◽  
Avian Origin ◽  
Canine Influenza

scholarly journals Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Hailiang Sun ◽  
Sherry Blackmon ◽  
Guohua Yang ◽  
Kaitlyn Waters ◽  
Tao Li ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Herd Immunity ◽  
Genetic Compatibility ◽  
Canine Influenza Virus ◽  
Canine Population ◽  
Avian Origin ◽  
Canine Influenza ◽  
Reassortant Viruses

ABSTRACT Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus (CIV) H3N2 (CIV-H3N2) and equine-origin CIV H3N8 (CIV-H3N8), are enzootic in the canine population. Dogs have been demonstrated to seroconvert in response to diverse IAVs, and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antiserum, we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting that there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2 × pandemic H1N1 (pdmH1N1) reassortants by characterizing their in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1, identifying some combinations that were more active than either parental virus complex. Using reverse genetics and fixing the CIV-H3N2 hemagglutinin (HA), we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high-growth phenotypes in vitro, and 13 of these replicated in mouse lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant was efficiently transmitted by contact but not by the airborne route and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs. IMPORTANCE IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained transmission into a human population with limited herd immunity. Dogs are a a potential mixing vessel for avian and mammalian IAVs and represent a human health concern due to their susceptibility to infection, large global population, and close physical contact with humans. Our results suggest that humans are likely to have limited preexisting immunity to CIV-H3N2 and that CIV-H3N2 × pdmH1N1 reassortants have moderate genetic compatibility and are transmissible by direct contact in ferrets. Our study contributes to the increasing evidence that surveillance of the canine population for IAVs is an important component of pandemic preparedness.

scholarly journals Influenza Viruses in Mice: Deep Sequencing Analysis of Serial Passage and Effects of Sialic Acid Structural Variation

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Brian R. Wasik ◽  
Ian E. H. Voorhees ◽  
Karen N. Barnard ◽  
Brynn K. Alford-Lawrence ◽  
Wendy S. Weichert ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Influenza A Virus ◽  
Deep Sequencing ◽  
Influenza A ◽  
Natural Host ◽  
H1n1 Pandemic ◽  
Influenza A Viruses ◽  
Canine Influenza Virus ◽  
Canine Influenza

ABSTRACT Influenza A viruses have regularly jumped to new host species to cause epidemics or pandemics, an evolutionary process that involves variation in the viral traits necessary to overcome host barriers and facilitate transmission. Mice are not a natural host for influenza virus but are frequently used as models in studies of pathogenesis, often after multiple passages to achieve higher viral titers that result in clinical disease such as weight loss or death. Here, we examine the processes of influenza A virus infection and evolution in mice by comparing single nucleotide variations of a human H1N1 pandemic virus, a seasonal H3N2 virus, and an H3N2 canine influenza virus during experimental passage. We also compared replication and sequence variation in wild-type mice expressing N-glycolylneuraminic acid (Neu5Gc) with those seen in mice expressing only N-acetylneuraminic acid (Neu5Ac). Viruses derived from plasmids were propagated in MDCK cells and then passaged in mice up to four times. Full-genome deep sequencing of the plasmids, cultured viruses, and viruses from mice at various passages revealed only small numbers of mutational changes. The H3N2 canine influenza virus showed increases in frequency of sporadic mutations in the PB2, PA, and NA segments. The H1N1 pandemic virus grew well in mice, and while it exhibited the maintenance of some minority mutations, there was no clear evidence for adaptive evolution. The H3N2 seasonal virus did not establish in the mice. Finally, there were no clear sequence differences associated with the presence or absence of Neu5Gc. IMPORTANCE Mice are commonly used as a model to study the growth and virulence of influenza A viruses in mammals but are not a natural host and have distinct sialic acid receptor profiles compared to humans. Using experimental infections with different subtypes of influenza A virus derived from different hosts, we found that evolution of influenza A virus in mice did not necessarily proceed through the linear accumulation of host-adaptive mutations, that there was variation in the patterns of mutations detected in each repetition, and that the mutation dynamics depended on the virus examined. In addition, variation in the viral receptor, sialic acid, did not affect influenza virus evolution in this model. Overall, our results show that while mice provide a useful animal model for influenza virus pathology, host passage evolution will vary depending on the specific virus tested.

Sign in / Sign up

Export Citation Format

Share Document