RESUMO
Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, the impact of the virus on glucose metabolism in host cells and the subsequent effects are still unknown. Here, glycolysis induced by SVA is shown to facilitate virus replication by promoting lactate production, which then attenuates the interaction between the mitochondrial antiviral-signaling protein (MAVS) and retinoic acid-inducible gene I (RIG-I). SVA induces glycolysis in PK-15 cells, as indicated by significantly increased expression of hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate kinase 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), and superoxide dismutase-2 (SOD2) in a dose-and replication-dependent manner, and enhanced lactate production, while reducing ATP generation. Overexpression of PKM, PGK1, HIF-1α, and PDK3 in PK-15 cells and high glucose concentrations promote SVA replication, while glycolytic inhibitors decrease it. Inhibition of RLR signaling allowed better replication of SVA by promoting lactate production to attenuate the interaction between MAVS and RIG-I, and regulatory effect of glycolysis on replication of SVA was mainly via RIG-I signaling. SVA infection in mice increased expression of PKM and PGK1 in tissues and serum yields of lactate. Mice treated with high glucose and administered sodium lactate showed elevated lactate levels and better SVA replication, as well as suppressed induction of RIG-I, interferon beta (IFNß), IFNα, interferon-stimulated gene 15 (ISG15), and interleukin 6 (IL-6). The inhibitory effect on interferons was lower in mice administered sodium oxamate and low glucose compared to the high glucose, indicating that RLR signaling was inhibited by SVA infection through lactate in vitro and in vivo. These results provide a new perspective on the relationship between metabolism and innate immunity of the host in SVA infection, suggesting that glycolysis or lactate may be new targets against the virus.
Assuntos
Glicólise , Ácido Láctico , Suínos , Camundongos , Animais , Replicação Viral , Glucose/metabolismoRESUMO
We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.
Assuntos
Antígenos Virais , Evolução Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Influenza Humana , Filogenia , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/imunologia , China/epidemiologia , Animais , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/imunologia , Antígenos Virais/imunologia , Antígenos Virais/genética , Aves/virologia , Variação AntigênicaRESUMO
Although reports of human infection with influenza A(H5N6) increased in 2021, reports of similar H5N6 virus infection in poultry are few. We detected 10 avian influenza A(H5N6) clade 2.3.4.4b viruses in poultry from 4 provinces in China. The viruses showed strong immune-escape capacity and complex genetic reassortment, suggesting further transmission risk.
Assuntos
Vírus da Influenza A , Influenza Aviária , Influenza Humana , Animais , Aves , China/epidemiologia , Humanos , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Influenza Humana/epidemiologia , Filogenia , Aves Domésticas , Vírus Reordenados/genéticaRESUMO
After a sharp decrease of influenza A(H7N9) virus in China in 2018, highly pathogenic H7N9 viruses re-emerged in 2019. These H7N9 variants exhibited a new predominant subclade and had been cocirculating at a low level in eastern and northeastern China. Several immune escape mutations and antigenic drift were observed in H7N9 variants.
Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Influenza Humana , Animais , China/epidemiologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/epidemiologiaRESUMO
Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant.IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed the molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found that all HPAIVs both are highly pathogenic and have valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, and transmissibility of these viruses to both poultry and mammals.
Assuntos
Doenças Transmissíveis Emergentes/virologia , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Influenza Aviária/virologia , Influenza Humana/virologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sítios de Ligação , Galinhas , Feminino , Variação Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Subtipo H7N9 do Vírus da Influenza A/classificação , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Influenza Aviária/mortalidade , Camundongos , Mutação , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/virologia , Filogenia , Ligação Proteica , VirulênciaRESUMO
Fourteen influenza A(H7N9) viruses were isolated from poultry or the environment in live poultry markets in Guangdong Province, China during 2014-2015. Phylogenetic analysis showed that all viruses were descended from viruses of the second wave of influenza A(H7N9) virus infections during 2013. These viruses can be divided into 2 branches.
Assuntos
Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Animais , China/epidemiologia , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Aviária/virologia , Filogenia , Aves DomésticasRESUMO
This study aimed to analyze the species and abundance of viruses carried by avian species in live poultry markets. In 2022, we collected 196 bird samples from two representative live poultry markets in Guangdong, China, of which 147 were randomly selected for metatranscriptome sequencing to construct a metatranscriptome library. This analysis yielded 17 viral families. Statistical analysis of the virus abundance of the six libraries showed that Picornaviridae, Retroviridae, Coronaviridae, and Othomyxoviridae were more abundant in the J1, J2, and J3 libraries, and Coronaviridae, Retroviridae, and Faviviridae were more abundant in the Y1, Y2, and E1 libraries. Finally, samples were screened using nested PCR and three viruses were identified. The positive results combined with high-throughput sequencing abundance data showed a positive correlation between virus abundance and the number of positive samples. This study provides scientific data to support the diagnosis and prevention of avian viral diseases.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Doenças das Aves Domésticas , Aves Domésticas , Vírus , Animais , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , China/epidemiologia , Aves Domésticas/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/epidemiologia , Vírus/genética , Vírus/isolamento & purificação , Vírus/classificação , Galinhas/virologiaRESUMO
H5-subtype avian influenza virus (AIV) is globally prevalent and undergoes frequent antigenic drift, necessitating regular updates to vaccines. One of the many influencing elements that cause incompatibility between vaccinations and epidemic strains is the dynamic alteration of glycosylation sites. However, the biological significance of N-glycosylation in the viral evolution and antigenic changes is unclear. Here, we performed a systematic analysis of glycosylation sites on the HA1 subunit of H5N1, providing insights into the changes of primary glycosylation sites, including 140 N, 156 N, and 170 N within the antigenic epitopes of HA1 protein. Multiple recombinant viruses were then generated based on HA genes of historical vaccine strains and deactivated for immunizing SPF chickens. Inactivated recombinant strains showed relatively closer antigenicity compared to which has identical N-glycosylation patterns. The N-glycosylation modification discrepancy highlights the inter-branch antigenic diversity of H5-subtype viruses in avian influenza and serves as a vital foundation for improving vaccination tactics.
Assuntos
Variação Antigênica , Galinhas , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Glicosilação , Animais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Galinhas/virologia , Influenza Aviária/imunologia , Influenza Aviária/virologia , Influenza Aviária/prevenção & controle , Virus da Influenza A Subtipo H5N1/imunologia , Virus da Influenza A Subtipo H5N1/genética , Vacinas contra Influenza/imunologia , Epitopos/imunologia , Epitopos/química , Antígenos Virais/imunologia , Antígenos Virais/genéticaRESUMO
The recent concurrent emergence of H5N1, H5N6, and H5N8 avian influenza viruses (AIVs) has led to significant avian mortality globally. Since 2020, frequent human-animal interactions have been documented. To gain insight into the novel H5 subtype AIVs (i.e., H5N1, H5N6 and H5N8), we collected 6102 samples from various regions of China between January 2021 and September 2022, and identified 41 H5Nx strains. Comparative analyses on the evolution and biological properties of these isolates were conducted. Phylogenetic analysis revealed that the 41 H5Nx strains belonged to clade 2.3.4.4b, with 13 related to H5N1, 19 to H5N6, and 9 to H5N8. Analysis based on global 2.3.4.4b viruses showed that all the viruses described in this study were likely originated from H5N8, exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015-2022 worldwide. H5N1 showed a higher rate of evolution in 2021-2022 and more sites under positive selection pressure in 2015-2022. The antigenic profiles of the novel H5N1 and H5N6 exhibited notable variations. Further hemagglutination inhibition assay suggested that some A(H5N1) viruses may be antigenically distinct from the circulating H5N6 and H5N8 strains. Mammalian challenge assays demonstrated that the H5N8 virus (21GD001_H5N8) displayed the highest pathogenicity in mice, followed by the H5N1 virus (B1557_H5N1) and then the H5N6 virus (220086_H5N6), suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian hosts. Based on the above results, we speculate that A(H5N1) viruses have a higher risk of emergence in the future. Collectively, these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.3.4.4b, contributing to a better understanding of designing more effective strategies for the prevention and control of novel H5 AIVs.
Assuntos
Evolução Molecular , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Filogenia , Animais , China/epidemiologia , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Camundongos , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Vírus da Influenza A Subtipo H5N8/genética , Vírus da Influenza A Subtipo H5N8/patogenicidade , Vírus da Influenza A Subtipo H5N8/classificação , Vírus da Influenza A Subtipo H5N8/isolamento & purificação , Virulência , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Vírus da Influenza A/classificação , Galinhas/virologia , Camundongos Endogâmicos BALB C , Feminino , Aves/virologia , HumanosRESUMO
H9N2 avian influenza viruses are endemic and persistent in China, but those that are prevalent in different provinces are also causes of wide epidemics, related to the spread of wild birds and the cross-regional trade in live poultry. For the past 4 years, beginning in 2018, we have sampled a live-poultry market in Foshan, Guangdong, in this ongoing study. In addition to the prevalence of H9N2 avian influenza viruses in China during this period, we identified isolates from the same market belonging to clade A and clade B, which diverged in 2012-2013, and clade C, which diverged in 2014-2016, respectively. An analysis of population dynamics revealed that, after a critical divergence period from 2014 to 2016, the genetic diversity of H9N2 viruses peaked in 2017. Our spatiotemporal dynamics analysis found that clade A, B, and C, which maintain high rates of evolution, have different prevalence ranges and transmission paths. Clades A and B were mainly prevalent in East China in the early stage, and then spread to Southern China, becoming epidemic with clade C. Strains from different regions converge at the same live-poultry market to communicate, which may be one reasons the H9N2 viruses are difficult to eradicate and increasingly dominant throughout China. Selection pressure and molecular analysis have demonstrated that single amino acid polymorphisms at key receptor binding sites 156, 160, and 190 under positive selection pressure, suggesting that H9N2 viruses are undergoing mutations to adapt to new hosts. Live-poultry markets are important because people who visit them have frequent contact with poultry, H9N2 viruses from different regions converge at these markets and spread through contact between live birds and humans, generating increased risks of human exposure to these viruses and threatening public health safety. Thus, it is important to reducing the cross-regional trade of live poultry and strengthening the monitoring of avian influenza viruses in live-poultry markets to reduce the spread of avian influenza viruses.
RESUMO
Influenza A viruses (IAV) have been a major cause of mortality. Given the potential for future deadly pandemics, effective drugs are needed for the treatment of severe influenzas, such as those caused by H5N1 IAV. The anti-malaria drugs artemisinin and its derivates, including artesunate (AS), have been reported to have broad antiviral activities. Here, we showed AS's antiviral activity against H5N1, H1N1, H3N2 and oseltamivir-resistant influenza A(H1N1)virus in vitro. Moreover, we showed that AS treatment significantly protected mice from lethal challenges with H1N1 and H5N1 IAV. Strikingly, the combination of AS and peramivir treatment significantly improved survival outcomes compared to their monotherapy with either AS or peramivir. Furthermore, we demonstrated mechanistically that AS affected the later stages of IAV replication and limited nuclear export of viral ribonucleoprotein (vRNP) complexes. In A549 cells, we demonstrated for the first time that AS treatment induced cAMP accumulation via inhibiting PDE4, and consequently reduced ERK phosphorylation and blocked IAV vRNP export, and thus suppressed IAV replication. These AS's effects were reversed by the pre-treatment with a cAMP inhibitor SQ22536. Our findings suggest that AS could serve as a novel IAV inhibitor by interfering vRNP nuclear export to prevent and treat IAV infection.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Humana , Animais , Camundongos , Humanos , Ribonucleoproteínas/metabolismo , Artesunato/farmacologia , Vírus da Influenza A Subtipo H1N1/metabolismo , Transporte Ativo do Núcleo Celular , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Replicação ViralRESUMO
BACKGROUND: ASF was first reported in Kenya in 1910 in 1921. In China, ASF spread to 31 provinces including Henan and Jiangsu within six months after it was first reported on August 3, 2018. The epidemic almost affected the whole China, causing direct economic losses of tens of billions of yuan. Cause great loss to our pig industry. As ELISA is cheap and easy to operate, OIE regards it as the preferred serological method for ASF detection. P54 protein has good antigenicity and is an ideal antigen for detection. OBJECTIVE: To identify a conservative site in the African swine fever virus (ASFV) p54 protein and perform a Cloth-enzyme-linked immunosorbent assay (ELISA) for detecting the ASFV antibody in order to reduce risks posed by using the live virus in diagnostic assays. METHOD: We used bioinformatics methods to predict the antigen epitope of the ASFV p54 protein in combination with the antigenic index and artificially synthesized the predicted antigen epitope peptides. Using ASFV-positive serum and specific monoclonal antibodies (mAbs), we performed indirect ELISA and blocking ELISA to verify the immunological properties of the predicted epitope polypeptide. RESULTS: The results of our prediction revealed that the possible antigen epitope regions were A23-29, A36-45, A72-94, A114-120, A124-130, and A137-150. The indirect ELISA showed that the peptides A23-29, A36-45, A72-94, A114-120, and A137-150 have good antigenicity. Moreover, the A36-45 polypeptide can react specifically with the mAb secreted by hybridoma cells, and its binding site contains a minimum number of essential amino acids in the sequence 37DIQFINPY44. CONCLUSIONS: Our study confirmed a conservative antigenic site in the ASFV p54 protein and its amino acid sequence. A competitive ELISA method for detecting ASFV antibodies was established based on recombinant p54 and matching mAb. Moreover, testing the protein sequence alignment verified that the method can theoretically detect antibodies produced by pigs affected by nearly all ASFVs worldwide.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Doenças dos Suínos , Febre Suína Africana/diagnóstico , Febre Suína Africana/epidemiologia , Vírus da Febre Suína Africana/genética , Animais , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Epitopos , Alinhamento de Sequência/veterinária , SuínosRESUMO
Seasonal H3N2 influenza virus has always been a potential threat to public health. The reassortment of the human and avian H3N2 influenza viruses has resulted in major influenza outbreaks, which have seriously damaged human life and health. To assess the possible threat of the H3N2 avian influenza virus to human health, we performed whole-genome sequencing and genetic evolution analyses on 10 H3N2 field strains isolated from different hosts and regions in 2019-2020 and selected representative strains for pathogenicity tests on mice. According to the results, the internal gene cassettes of nine strains had not only undergone reassortment with the H1, H2, H4, H6, and H7 subtypes, which circulate in poultry and mammals, but also with H10N8, which circulates in wild birds in the natural environment. Three reassorted strains were found to be pathogenic to mice, of these one strain harboring MP from H10N8 showed a stronger virulence in mice. This study indicates that reassorted H3N2 AIVs may cross the host barrier to infect mammals and humans, thereby, necessitating persistent surveillance of H3N2 AIVs.
Assuntos
Vírus da Influenza A , Influenza Aviária , Influenza Humana , Humanos , Camundongos , Animais , Vírus da Influenza A Subtipo H3N2/genética , Virulência , Vírus Reordenados , Genoma Viral , Filogenia , Influenza Humana/epidemiologia , Influenza Humana/genética , MamíferosRESUMO
The H5N1 and H9N2 avian influenza viruses (AIVs) seriously endanger the poultry industry and threaten human health. Characteristic inflammatory responses caused by H5N1 and H9N2 AIVs in birds and mammals result in unique clinical manifestations. The role of anti-inflammatory regulators, PTX3, Del-1, and GDF-15, in H5N1 and H9N2-AIV-mediated inflammation in birds and mammals has not yet been verified. Here, the expression of PTX3, Del-1, and GDF-15 in DF-1 and MDCK cells infected with H5N1 and H9N2 AIVs and their effect on inflammatory cytokines were analyzed. Infection with both AIVs increased PTX3, Del-1, and GDF-15 expression in DF-1 and MDCK cells. Infection with H9N2 or H5N1 AIV in DF-1 and MDCK cells with overexpression of all three factors, either alone or in combination, inhibited the expression of tested inflammatory cytokines. Furthermore, co-expression of PTX3, Del-1, and GDF-15 enhanced the inhibition, irrespective of the cell line. The findings from this study offer insight into the pathogenic differences between H5N1 and H9N2 AIVs in varied hosts. Moreover, our findings can be used to help screen for host-specific anti-inflammatory agents.
Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Animais , Galinhas , Citocinas , Cães , Humanos , Inflamação , Células Madin Darby de Rim Canino , MamíferosRESUMO
African swine fever virus (ASFV) is a highly infectious and lethal swine pathogen that causes severe socio-economic consequences in affected countries. Unfortunately, effective vaccine for combating ASF is unavailable so far, and the prevention and control strategies for ASFV are still very limited. Toosendanin (TSN), a triterpenoid saponin extracted from the medicinal herb Melia toosendan Sieb. Et Zucc, has been demonstrated to possess analgesic, anti-inflammatory, anti-botulism and anti-microbial activities, and was used clinically as an anthelmintic, while the antiviral effect of TSN on ASFV has not been reported. In this study, we revealed that TSN exhibited a potent inhibitory effect on ASFV GZ201801-38 strain in porcine alveolar macrophages (PAMs; EC50 = 0.085 µM, SI = 365) in a dose-dependent manner. TSN showed robust antiviral activity in different doses of ASFV infection and reduced the transcription and translation levels of ASFV p30 protein, viral genomic DNA quantity as well as viral titer at 24 and 48 h post-infection. In addition, TSN did not affect virion attachment and release but intervened in its internalization in PAMs. Further investigations disclosed that TSN played its antiviral role by upregulating the host IFN-stimulated gene (ISG) IRF1 rather than by directly inactivating the virus particles. Overall, our results suggest that TSN is an effective antiviral agent against ASFV replication in vitro and may have the potential for clinical use.
RESUMO
In early 2021, roughly 6 months after the H7N9 H7-Re3 and H7N9 rLN79 vaccine strains were introduced into China, we monitored a number of H7N9 subtype avian influenza viruses, which could have escaped vaccine-induced immunity in live poultry markets (LPMs) in Yunnan, Hebei, Shanxi and Guangdong provinces, China. To investigate whether these viruses were a novel H7N9 variant of highly pathogenic avian influenza (HPAI) virus and whether they had the potential for further spread, we characterized the genetic evolution, antigenic divergence and pathogenicity of the viruses in the context of vaccine immunity. The results show further diversification in the HA gene of newly isolated HPAI H7N9 viruses compared with antigenic variants that emerged after the period of 2017-2019. There were clear antigenic differences between current vaccines and these viruses, and SPF broilers under vaccine protection could not resist virus challenges. Our study demonstrates that the current vaccine has insufficient protective capacity against the novel H7N9 variants under experimental conditions. A novel H7N9 immune escape virus has emerged. Faced with potential outbreaks, we should strengthen surveillance and update vaccine strains.
Assuntos
Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Aviária , Influenza Humana , Vacinas , Animais , Galinhas , China/epidemiologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Influenza Aviária/epidemiologia , Influenza Aviária/prevenção & controleAssuntos
Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Vírus Reordenados , Animais , China/epidemiologia , História do Século XXI , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/história , Influenza Humana/transmissãoRESUMO
No avian H7N9 outbreaks have occurred since the introduction of H7N9 inactivated vaccine in the fall of 2017. However, H7N9 is still prevalent in poultry. To surveil the prevalence, genetic characteristics, and antigenic changes of H7N9, over 7000 oropharyngeal and cloaca swab specimens were collected from live poultry markets and farms in 15 provinces of China from 2017 to 2019. A total of 85 influenza virus subtype H7N9 strains were isolated and 20 representative strains were selected for genetic analysis and antigenicity evaluation. Results indicated the decreased prevalence of low-pathogenic H7N9 strains while highly-pathogenic H7N9 strains became dominated since the introduction of vaccine. Phylogenetic analysis showed that strains from 2019 formed an independent small branch and were genetically distant to strains isolated in 2013-2018. Analysis of key amino acid sites showed that the virus strains may adapt to the host environment evolutionally through mutation. Our analysis predicted additional potential glycosylation sites for HA and NA genes in the 2019 strains. Sequence analysis of HA gene in strains isolated from 2018 to 2019 showed that there were an increased nucleotide substitution rate and an increased mutation rate in the first and second nucleotides of coding codons within the open reading frame. The hemagglutination inhibition (HI) assay showed that H7-Re1 and H7-Re2 exhibited a lower HI titer for isolates from 2019, while H7-Re3 and rLN79 showed a high HI titer. The protective effect of the vaccine decreased after 15 months of use. Overall, under vaccination pressure, the evolution of influenza virus subtype H7N9 has accelerated.
Assuntos
Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Aviária , Influenza Humana , Animais , China/epidemiologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/prevenção & controle , Filogenia , VacinaçãoRESUMO
Multiple recent outbreaks of highly pathogenic H5N8 viruses originating in aquatic birds frequently occurred in most European countries, Russia, South Korea, and Japan during the winter of 2020-21, and one zoonotic event of poultry workers infected with novel H5N8 viruses were reported in Russia. Strikingly, these novel H5N8 viruses had emerged and been co-circulating in wild birds and poultry in multiple provinces of China during 2020-21. In China, the population of aquatic birds has risen significantly in the past twenty years, and China is regarded as the largest reservoir for influenza viruses carried in aquatic birds across the globe. Hence, the co-circulation of these novel H5N8 viruses poses an alarming threat to not only poultry industry but also human health. In this study, we sequenced full-length genomes of these H5N8 viruses circulating in China. Phylogenetic analysis demonstrated that poultry-origin H5N8 viruses in China fell within wild birds-origin clade 2.3.4.4b H5N8 viruses from Europe during 2020-21, and notably, were genetically closely related to human-infecting H5N8 viruses in Russia. Moreover, they possessed several molecular markers associated with mammalian adaption. Bayesian coalescent analysis showed that these H5N8 viruses might have introduced into China during June-September 2020, suggesting that these H5N8 viruses might have introduced via wild bird migration or poultry trade. Besides, we also found that the effective population size of clade 2.3.4.4b H5N8 viruses dramatically increased during the winter season of 2020/21, as is consistent with previous increase of genetic diversity during the winter seasons of 2013/14 and 2016/17, which indicated that the wild bird migration accelerates the genetic diversity of these H5N8 viruses during the winter season of 2020/21. Notably, these novel H5N8 viruses were lethal to chickens and mice, highly transmissible to ducks, and were antigenically distinct from 2.3.4.4h H5 viruses circulating in China, posing considerable threats to public health. Our findings offer novel insights into the evolution and risk assessment of H5N8 viruses during the winter season of 2020-21.