Evolution of the hemagglutinin gene of H3N8 canine influenza virus in dogs.
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ABSTRACT:
SUBMITTER: Pecoraro HL
PROVIDER: S-EPMC4232753 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundH3N8 canine influenza virus (CIV) infection might contribute to increased duration of shelter stay for dogs. Greater understanding of factors contributing to CIV within shelters could help veterinarians identify control measures for CIV.ObjectivesTo assess community to shelter dog CIV transmission, estimate true prevalence of CIV, and determine risk factors associated with CIV in humane shelters.Animals5,160 dogs upon intake or discharge from 6 US humane shelters, December 2009 through January 2012.MethodsA cross-sectional study was performed with prospective convenience sampling of 40 dogs from each shelter monthly. Nasal swabs and serum samples were collected. Hemagglutination inhibition and real-time reverse transcriptase-polymerase chain reaction assays were performed for each nasal and serum sample. True prevalence was estimated by stochastic latent class analysis. Logistic regression was used to identify risk factors associated with CIV shedding and seropositivity.ResultsNasal swabs were positive from 4.4% of New York (NY), 4.7% of Colorado (CO), 3.2% of South Carolina, 1.2% of Florida, and 0% of California and Texas shelter dogs sampled. Seropositivity was the highest in the CO shelter dogs at 10%, and NY at 8.5%. Other shelters had 0% seropositivity. Information-theoretic analyses suggested that CIV shedding was associated with region, month, and year (model weight = 0.95) and comingling/cohousing (model weight = 0.92).Conclusions and clinical importanceCommunity dogs are a likely source of CIV introduction into humane shelters and once CIV has become established, dog-to-dog transmission maintains the virus within a shelter.
| S-EPMC4857996 | biostudies-literature
Project description:Equine H3N8 influenza A viruses (EIVs) cause respiratory disease in horses and circulate among horses worldwide. In 2004, an outbreak of canine H3N8 influenza A virus (CIV) occurred among dogs in Florida and has spread among dogs in the United States (US). Genetic analyses revealed that this CIV is closely related to the recent EIVs. Although CIV-infected dogs could be the source of H3N8 influenza A virus for horses, it remains unclear whether the CIV circulating in the United States still maintains its infectivity and/or pathogenicity in horses. To address this, we investigated the infectivity and pathogenicity of CIV in horses and the receptor binding specificity of CIV.Three horses were inoculated with A/canine/Colorado/30604/2006 (CO06, H3N8). Clinical signs and nasal swabs were recorded or collected every day. We also evaluated the virus binding to α2-3-linked 5-N-acetylneuraminic acid (NeuAcα2-3Gal) and 5-N-glycolylneuraminic acid (NeuGcα2-3Gal) receptor analogues.Although all the three horses inoculated with CO06 seroconverted, they showed only mild clinical signs and two of them showed no virus shedding. CO06 had reduced binding to NeuGcα2-3Gal.Our results demonstrated that CO06 had reduced proliferation ability and pathogenicity in horses. As the recognition of NeuGcα2-3Gal by EIV is known to be essential for binding to the equine respiratory system, the decreased binding of CO06 to NeuGcα2-3Gal may be one of the important factors that reduces the proliferation ability and pathogenicity of CO06 in horses.
| S-EPMC4634615 | biostudies-other
Project description:In 2004, canine influenza virus subtype H3N8 emerged in greyhounds in the United States. Subsequent serologic evidence indicated virus circulation in dog breeds other than greyhounds, but the virus had not been isolated from affected animals. In 2005, we conducted virologic investigation of 7 nongreyhound dogs that died from respiratory disease in Florida and isolated influenza subtype H3N8 virus. Antigenic and genetic analysis of A/canine/Jacksonville/2005 (H3N8) and A/canine/Miami/2005 (H3N8) found similarity to earlier isolates from greyhounds, which indicates that canine influenza viruses are not restricted to greyhounds. The hemagglutinin contained 5 conserved amino acid differences that distinguish canine from equine lineages. The antigenic homogeneity of the canine viruses suggests that measurable antigenic drift has not yet occurred. Continued surveillance and antigenic analyses should monitor possible emergence of antigenic variants of canine influenza virus.
| S-EPMC2600298 | biostudies-literature
Project description:An outbreak of respiratory disease caused by the equine-origin influenza A(H3N8) virus was first detected in dogs in 2004 and since then has been enzootic among dogs. Currently, the molecular mechanisms underlying host adaption of this virus from horses to dogs is unknown. Here, we have applied quantitative binding, growth kinetics, and immunofluorescence analyses to elucidate these mechanisms. Our findings suggest that a substitution of W222L in the hemagglutinin of the equine-origin A(H3N8) virus facilitated its host adaption to dogs. This mutation increased binding avidity of the virus specifically to receptor glycans with N-glycolylneuraminic acid (Neu5Gc) and sialyl Lewis X (SLeX) motifs. We have demonstrated these motifs are abundantly located in the submucosal glands of dog trachea. Our findings also suggest that in addition to the type of glycosidic linkage (e.g., ?2,3-linkage or ?2,6-linkage), the type of sialic acid (Neu5Gc or 5-N-acetyl neuraminic acid) and the glycan substructure (e.g., SLeX) also play an important role in host tropism of influenza A viruses.IMPORTANCE Influenza A viruses (IAVs) cause a significant burden on human and animal health, and mechanisms for interspecies transmission of IAVs are far from being understood. Findings from this study suggest that an equine-origin A(H3N8) IAV with mutation W222L at its hemagglutinin increased binding to canine-specific receptors with sialyl Lewis X and Neu5Gc motifs and, thereby, may have facilitated viral adaption from horses to dogs. These findings suggest that in addition to the glycosidic linkage (e.g., ?2,3-linked and ?2,6-linked), the substructure in the receptor saccharides (e.g., sialyl Lewis X and Neu5Gc) could present an interspecies transmission barrier for IAVs and drive viral mutations to overcome such barriers.
| S-EPMC6146684 | biostudies-literature
Project description:BackgroundSince equine influenza A virus (H3N8) was transmitted to dogs in the United States in 2004, the causative virus, which is called canine influenza A virus (CIV), has become widespread in dogs. To date, it has remained unclear whether or not CIV-infected dogs could transmit CIV to horses. To address this, we tested whether or not close contact between horses and dogs experimentally infected with CIV would result in its interspecies transmission.MethodsThree pairs of animals consisting of a dog inoculated with CIV (10(8.3) egg infectious dose 50/dog) and a healthy horse were kept together in individual stalls for 15 consecutive days. During the study, all the dogs and horses were clinically observed. Virus titres in nasal swab extracts and serological responses were also evaluated. In addition, all the animals were subjected to a gross pathological examination after euthanasia.ResultsAll three dogs inoculated with CIV exhibited clinical signs including, pyrexia, cough, nasal discharge, virus shedding and seroconversion. Gross pathology revealed lung consolidations in all the dogs, and Streptococcus equi subsp. zooepidemicus was isolated from the lesions. Meanwhile, none of the paired horses showed any clinical signs, virus shedding or seroconversion. Moreover, gross pathology revealed no lesions in the respiratory tracts including the lungs of the horses.ConclusionsThese findings may indicate that a single dog infected with CIV is not sufficient to constitute a source of CIV infection in horses.
| S-EPMC3416777 | biostudies-literature
Project description:The "Spanish" influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in 1918. Influenza RNA was also isolated from lung tissue samples from two additional victims of the lethal 1918 influenza: one formalin-fixed, paraffin-embedded sample and one frozen sample obtained by in situ biopsy of the lung of a victim buried in permafrost since 1918. The complete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/New York/1/18 and A/Brevig Mission/1/18). The sequences show little variation. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918.
| S-EPMC15547 | biostudies-literature
Project description:Equine influenza viruses (EIVs) of the H3N8 and H7N7 subtypes are the causative agents of an important disease of horses. While EIV H7N7 apparently is extinct, H3N8 viruses have circulated for more than 50 years. Like human influenza viruses, EIV H3N8 caused a transcontinental pandemic followed by further outbreaks and epidemics, even in populations with high vaccination coverage. Recently, EIV H3N8 jumped the species barrier to infect dogs. Despite its importance as an agent of infectious disease, the mechanisms that underpin the evolutionary and epidemiological dynamics of EIV are poorly understood, particularly at a genomic scale. To determine the evolutionary history and phylodynamics of EIV H3N8, we conducted an extensive analysis of 82 complete viral genomes sampled during a 45-year span. We show that both intra- and intersubtype reassortment have played a major role in the evolution of EIV, and we suggest that intrasubtype reassortment resulted in enhanced virulence while heterosubtypic reassortment contributed to the extinction of EIV H7N7. We also show that EIV evolves at a slower rate than other influenza viruses, even though it seems to be subject to similar immune selection pressures. However, a relatively high rate of amino acid replacement is observed in the polymerase acidic (PA) segment, with some evidence for adaptive evolution. Most notably, an analysis of viral population dynamics provided evidence for a major population bottleneck of EIV H3N8 during the 1980s, which we suggest resulted from changes in herd immunity due to an increase in vaccination coverage.
| S-EPMC3094979 | biostudies-literature
Project description:Equine Influenza virus H3N8 Targeted Locus segment 4 hemagglutinin
| PRJNA274313 | ENA
Project description: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.
| S-EPMC7375373 | biostudies-literature
Project description: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.
| S-EPMC5660486 | biostudies-literature