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1.
Euro Surveill ; 25(4)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32019669

RESUMO

Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4-3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Surtos de Doenças/estatística & dados numéricos , Pneumonia Viral/transmissão , Síndrome Respiratória Aguda Grave/transmissão , Replicação Viral , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Saúde Global , Humanos , Controle de Infecções , Vírus da Influenza A/patogenicidade , Influenza Humana/transmissão , Pandemias , Pneumonia Viral/epidemiologia , Risco , Vírus da SARS/patogenicidade
2.
Nat Commun ; 11(1): 164, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919360

RESUMO

Host dependency factors that are required for influenza A virus infection may serve as therapeutic targets as the virus is less likely to bypass them under drug-mediated selection pressure. Previous attempts to identify host factors have produced largely divergent results, with few overlapping hits across different studies. Here, we perform a genome-wide CRISPR/Cas9 screen and devise a new approach, meta-analysis by information content (MAIC) to systematically combine our results with prior evidence for influenza host factors. MAIC out-performs other meta-analysis methods when using our CRISPR screen as validation data. We validate the host factors, WDR7, CCDC115 and TMEM199, demonstrating that these genes are essential for viral entry and regulation of V-type ATPase assembly. We also find that CMTR1, a human mRNA cap methyltransferase, is required for efficient viral cap snatching and regulation of a cell autonomous immune response, and provides synergistic protection with the influenza endonuclease inhibitor Xofluza.


Assuntos
Predisposição Genética para Doença/genética , Interações Hospedeiro-Patógeno/genética , Vírus da Influenza A/patogenicidade , Influenza Humana/genética , Influenza Humana/patologia , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/genética , Antivirais/farmacologia , Sistemas CRISPR-Cas , Linhagem Celular , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Estudo de Associação Genômica Ampla , Humanos , Proteínas de Membrana/genética , Metiltransferases/metabolismo , Proteínas do Tecido Nervoso/genética , Oxazinas/farmacologia , Piridinas/farmacologia , Tiepinas/farmacologia , Triazinas/farmacologia , ATPases Vacuolares Próton-Translocadoras/metabolismo , Internalização do Vírus
3.
J Pharm Biomed Anal ; 177: 112876, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525575

RESUMO

Flavonoids-enriched extract from Scutellaria baicalensis roots (FESR) ameliorated influenza A virus (IAV) induced acute lung injury (ALI) in mice by inhibiting the excessive activation of complement system in vivo. However, FESR had no anti-complementary activity in vitro. In order to reveal the effective materials of FESR for the treatment of IAV-induced ALI, the present research explored the metabolic process of FESR both in nomal and IAV infected mice by the method of UHPLC-ESI-LTQ/MS, as well as the metabolic activating mechanism. The results showed that the inactive flavonoid glycosides of FESR were partly metabolized into anti-complementary aglycones in vivo, mainly including 5,7,4'-trihydroxy-8-methoxy-flavone, norwogonin, baicalein, wogonin, oroxylin A and chrysin. Moreover, compared with the normal mice, IAV-induced ALI mice exhibited more efficient on producing and absorbing these active metabolites, with AUC0-t and Cmax in plasma and concentrations in lungs and intestines markedly elevated in the IAV treated groups (P <  0.05). Interestingly, the intestinal bacteria from IAV-induced ALI mice showed stronger ß-glucuronidase activity and also had higher efficiency on transforming FESR to the flavonoid aglycones. These findings suggested that the anti-complementary aglycones produced by metabolic activation in vivo should be the potential effective materials of FESR against IAV infections, and intestinal bacteria might play an important role on the higher bioavailability of FESR in IAV infected mice. Additionally, the animals under the pathological state are more suitable for the metabolic study of traditional Chinese medicine.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Inativadores do Complemento/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Influenza Humana/tratamento farmacológico , Scutellaria baicalensis/química , Ativação Metabólica , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/virologia , Animais , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Flavonoides/administração & dosagem , Microbioma Gastrointestinal/fisiologia , Glucuronidase/metabolismo , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Influenza Humana/metabolismo , Influenza Humana/virologia , Pulmão/patologia , Camundongos , Raízes de Plantas/química , Organismos Livres de Patógenos Específicos
4.
Biochimie ; 166: 203-213, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518617

RESUMO

Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A , Influenza Humana , Serina Proteases/fisiologia , Internalização do Vírus/efeitos dos fármacos , Animais , Galinhas/virologia , Citocinas/metabolismo , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/patogenicidade , Influenza Aviária/tratamento farmacológico , Influenza Aviária/virologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Tripsina/metabolismo
5.
Virus Genes ; 55(6): 815-824, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549291

RESUMO

Viruses are believed to be ubiquitous; however, the diversity of viruses is largely unknown because of the bias of previous research toward pathogenic viruses. Deep sequencing is a promising and unbiased approach to detect viruses from animal-derived materials. Although cranes are known to be infected by several viruses such as influenza A viruses, previous studies targeted limited species of viruses, and thus viruses that infect cranes have not been extensively studied. In this study, we collected crane fecal samples in the Izumi plain in Japan, which is an overwintering site for cranes, and performed metagenomic shotgun sequencing analyses. We detected aviadenovirus-like sequences in the fecal samples and tentatively named the discovered virus crane-associated adenovirus 1 (CrAdV-1). We determined that our sequence accounted for approximately three-fourths of the estimated CrAdV-1 genome size (33,245 bp). The GC content of CrAdV-1 genome is 34.1%, which is considerably lower than that of other aviadenoviruses. Phylogenetic analyses revealed that CrAdV-1 clusters with members of the genus Aviadenovirus, but is distantly related to the previously identified aviadenoviruses. The protein sequence divergence between the DNA polymerase of CrAdV-1 and those of other aviadenoviruses is 45.2-46.8%. Based on these results and the species demarcation for the family Adenoviridae, we propose that CrAdV-1 be classified as a new species in the genus Aviadenovirus. Results of this study contribute to a deeper understanding of the diversity and evolution of viruses and provide additional information on viruses that infect cranes, which might lead to protection of the endangered species of cranes.


Assuntos
Infecções por Adenoviridae/genética , Aviadenovirus/genética , Doenças das Aves/genética , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/isolamento & purificação , Doenças das Aves/virologia , Aves/genética , Aves/virologia , Fezes/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Japão , Filogenia
6.
Am J Chin Med ; 47(6): 1307-1324, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31505936

RESUMO

Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its underlying mechanisms of action and constituents have not yet been completely elucidated. Previously, we have confirmed that AVE treatment significantly reduces the viral replication of green fluorescent protein-labeled influenza A virus in Madin-Darby canine kidney (MDCK) cells. In addition, post-treatment with AVE inhibited viral matrix protein 1 (M1), matrix protein 2 (M2), and hemagglutinin (HA) mRNA synthesis and viral protein (M1, M2, and HA) expressions. In this study, we demonstrated that AVE inhibited autophagy induced by influenza A virus in MDCK cells and also identified quercetin, catechin hydrate, and kaempferol as the active antiviral components of AVE. We also found that post-treatment with quercetin, catechin hydrate, and kaempferol markedly inhibited M2 viral mRNA synthesis and M2 protein expression. A docking simulation suggested that the binding affinity of quercetin, catechin hydrate, and kaempferol for the M2 protein may be higher than that of known M2 protein inhibitors. Thus, the inhibition of autophagy induced by influenza virus may explain the antiviral activity of AVE against H1N1 or H3N2. Aloe vera extract and its constituents may, therefore, be potentially useful for the development of anti-influenza agents.


Assuntos
Aloe/química , Antivirais , Autofagia/efeitos dos fármacos , Vírus da Influenza A/fisiologia , Vírus da Influenza A/patogenicidade , Extratos Vegetais/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Células Cultivadas , Cães , Hemaglutininas Virais/genética , Hemaglutininas Virais/metabolismo , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza A/metabolismo , Rim/citologia , Ligação Proteica/efeitos dos fármacos , Quercetina/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Proteínas da Matriz Viral/metabolismo
7.
PLoS Pathog ; 15(9): e1008077, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31557273

RESUMO

Influenza A virus (IAV) is a seasonal pathogen with the potential to cause devastating pandemics. IAV infects multiple epithelial cell subsets in the respiratory tract, eliciting damage to the lungs. Clearance of IAV is primarily dependent on CD8+ T cells, which must balance control of the infection with immunopathology. Using a virus expressing Cre recombinase to permanently label infected cells in a Cre-inducible reporter mouse, we previously discovered infected club cells that survive both lytic virus replication and CD8+ T cell-mediated clearance. In this study, we demonstrate that ciliated epithelial cells, type I and type II alveolar cells can also become survivor cells. Survivor cells are stable in the lung long-term and demonstrate enhanced proliferation compared to uninfected cells. When we investigated how survivor cells evade CD8+ T cell killing we observed that survivor cells upregulated the inhibitory ligand PD-L1, but survivor cells did not use PD-L1 to evade CD8+ T cell killing. Instead our data suggest that survivor cells are not inherently resistant to CD8+ T cell killing, but instead no longer present IAV antigen and cannot be detected by CD8+ T cells. Finally, we evaluate the failure of CD8+ T cells to kill these previously infected cells. This work demonstrates that additional cell types can survive IAV infection and that these cells robustly proliferate and are stable long term. By sparing previously infected cells, the adaptive immune system may be minimizing pathology associated with IAV infection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Evasão da Resposta Imune , Influenza Humana/imunologia , Influenza Humana/virologia , Imunidade Adaptativa , Animais , Antígeno B7-H1/imunologia , Proliferação de Células , Sobrevivência Celular/imunologia , Citotoxicidade Imunológica , Humanos , Imunidade Celular , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Influenza Humana/patologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptor de Morte Celular Programada 1/imunologia
8.
Zoonoses Public Health ; 66(7): 874-878, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31493311

RESUMO

We estimated that more than 11,000 people were exposed to highly pathogenic avian influenza viruses in EU/EEA countries over the outbreak period October 2016-September 2018 by cross-linking data submitted by Member States to European Food Safety Authority and EMPRES-i. A stronger framework for collecting human exposure data is required.


Assuntos
Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Animais , Animais Selvagens/virologia , Aves/virologia , União Europeia , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/patogenicidade , Influenza Aviária/epidemiologia
9.
BMC Infect Dis ; 19(1): 676, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370782

RESUMO

BACKGROUND: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings. The objective of this study was to develop and optimized a multiplex detection system for most influenza viruses currently infecting humans. METHODS: We developed and optimized a multiplex detection system for most influenza viruses currently infecting humans including two type B (both Victoria lineages and Yamagata lineages), H1N1, H3N2, H5N1, H5N6, and H7N9 using Reverse Transcriptional Loop-mediated Isothermal Amplification (RT-LAMP) technology coupled with a one-pot colorimetric visualization system to facilitate direct determination of results without additional steps. We also evaluated this multiplex RT-LAMP for clinical use using a total of 135 clinical and spiked samples (91 influenza viruses and 44 other human infectious viruses). RESULTS: We achieved rapid detection of seasonal influenza viruses (H1N1, H3N2, and Type B) and avian influenza viruses (H5N1, H5N6, H5N8 and H7N9) within an hour. The assay could detect influenza viruses with high sensitivity (i.e., from 100 to 0.1 viral genome copies), comparable to conventional RT-PCR-based approaches which would typically take several hours and require expensive equipment. This assay was capable of specifically detecting each influenza virus (Type B, H1N1, H3N2, H5N1, H5N6, H5N8 and H7N9) without cross-reactivity with other subtypes of AIVs or other human infectious viruses. Furthermore, 91 clinical and spiked samples confirmed by qRT-PCR were also detected by this multiplex RT-LAMP with 98.9% agreement. It was more sensitive than one-step RT-PCR approach (92.3%). CONCLUSIONS: Results of this study suggest that our multiplex RT-LAMP assay may provide a rapid, sensitive, cost-effective, and reliable diagnostic method for identifying recent influenza viruses infecting humans, especially in locations without access to large platforms or sophisticated equipment.


Assuntos
Colorimetria/métodos , Vírus da Influenza A/genética , Influenza Humana/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Reações Cruzadas , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Virus da Influenza A Subtipo H5N1/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Transcrição Reversa
10.
PLoS Pathog ; 15(8): e1007892, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31415678

RESUMO

The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of isogenic viruses that carry avian- or human-derived M segments. Avian, but not human, M segments restricted viral growth and transmission in mammalian model systems, and the restricted growth correlated with increased expression of M2 relative to M1. M2 overexpression was associated with intracellular accumulation of autophagosomes, which was alleviated by interference of the viral proton channel activity by amantadine treatment. As M1 and M2 are expressed from the M mRNA through alternative splicing, we separated synonymous and non-synonymous changes that differentiate human and avian M segments and found that dysregulation of gene expression leading to M2 overexpression diminished replication, irrespective of amino acid composition of M1 or M2. Moreover, in spite of efficient replication, virus possessing a human M segment that expressed avian M2 protein at low level did not transmit efficiently. We conclude that (i) determinants of transmission reside in the IAV M2 protein, and that (ii) control of M segment gene expression is a critical aspect of IAV host adaptation needed to prevent M2-mediated dysregulation of vesicular homeostasis.


Assuntos
Aves/virologia , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Proteínas da Matriz Viral/metabolismo , Replicação Viral , Células A549 , Animais , Cães , Feminino , Cobaias , Humanos , Influenza Humana/genética , Influenza Humana/metabolismo , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/metabolismo , Especificidade da Espécie , Proteínas da Matriz Viral/genética
11.
Transbound Emerg Dis ; 66(6): 2411-2425, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31328387

RESUMO

Since 2014, H5 highly pathogenic avian influenza viruses (HPAIVs) from clade 2.3.4.4 have been persistently circulating in Southern China. This has caused huge losses in the poultry industry. In this study, we analysed the genetic characteristics of seven H5N6 HPAIVs of clade 2.3.4.4 that infected birds in Southern China in 2016. Phylogenetic analysis grouped the HA, PB2, PA, M and NS genes as MIX-like, and the NA genes grouped into the Eurasian lineage. The PB1 genes of the GS24, GS25, CK46 and GS74 strains belonged to the VN 2014-like group and the others were grouped as MIX-like. The NP genes of GS24 and GS25 strains belonged to the ZJ-like group, but the others were MIX-like. Thus, these viruses came from different genotypes, and the GS24, GS25, CK46 and GS74 strains displayed genotype recombination. Additionally, our results showed that the mean death time of all chickens inoculated with 105 EID50 of CK46 or GS74 viruses was 3 and 3.38 days, respectively. The viruses replicated at high titers in all tested tissues of the inoculated chickens. They also replicated in all tested tissues of naive contact chickens, but their replication titers in some tissues were significantly different (p < 0.05). Thus, the viruses displayed high pathogenicity and variable transmission in chickens. Therefore, it is necessary to focus on the pathogenic variation and molecular evolution of H5N6 HPAIVs in order to prevent and control avian influenza in China.


Assuntos
Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Aviária/transmissão , Animais , Galinhas/virologia , China , Evolução Molecular , Genótipo , Vírus da Influenza A/classificação , Filogenia , Recombinação Genética , Replicação Viral
12.
Nat Microbiol ; 4(11): 1964-1977, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31358986

RESUMO

Despite the cytopathic nature of influenza A virus (IAV) replication, we recently reported that a subset of lung epithelial club cells is able to intrinsically clear the virus and survive infection. However, the mechanisms that drive cell survival during a normally lytic infection remained unclear. Using a loss-of-function screening approach, we discovered that the DNA mismatch repair (MMR) pathway is essential for club cell survival of IAV infection. Repair of virally induced oxidative damage by the DNA MMR pathway not only allowed cell survival of infection, but also facilitated host gene transcription, including the expression of antiviral and stress response genes. Enhanced viral suppression of the DNA MMR pathway prevented club cell survival and increased the severity of viral disease in vivo. Altogether, these results identify previously unappreciated roles for DNA MMR as a central modulator of cellular fate and a contributor to the innate antiviral response, which together control influenza viral disease severity.


Assuntos
Reparo de Erro de Pareamento de DNA , Redes Reguladoras de Genes , Imunidade Inata , Vírus da Influenza A/patogenicidade , Influenza Humana/genética , Células A549 , Animais , Linhagem Celular , Modelos Animais de Doenças , Cães , Regulação da Expressão Gênica , Humanos , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Células Madin Darby de Rim Canino , Camundongos , Estresse Oxidativo , Replicação Viral
13.
Transbound Emerg Dis ; 66(6): 2209-2217, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31309743

RESUMO

Since 2013, H5N6 highly pathogenic avian influenza viruses (HPAIVs) have been responsible for outbreaks in poultry and wild birds around Asia. H5N6 HPAIV is also a public concern due to sporadic human infections being reported in China. In the current study, we isolated an H5N6 HPAIV strain (A/Muscovy duck/Long An/AI470/2018; AI470) from an outbreak at a Muscovy duck farm in Long An Province in Southern Vietnam in July 2018 and genetically characterized it. Basic Local Alignment Search Tool (BLAST) analysis revealed that the eight genomic segments of AI470 were most closely related (99.6%-99.9%) to A/common gull/Saratov/1676/2018 (H5N6), which was isolated in October 2018 in Russia. Furthermore, AI470 also shared 99.4%-99.9% homology with A/Guangxi/32797/2018, an H5N6 HPAIV strain that infected humans in China in 2018. Phylogenetic analyses of the entire genome showed that AI470 was directly derived from H5N6 HPAIVs that were in South China from 2015 to 2018 and clustered with four H5N6 HPAIV strains of human origin in South China from 2017 to 2018. This indicated that AI470 was introduced into Vietnam from China. In addition, molecular characteristics related to mammalian adaptation among the recent human H5N6 HPAIV viruses, except PB2 E627K, were shared by AI470. These findings are cause for concern since H5N6 HPAIV strains that possess a risk of human infection have crossed the Chinese border.


Assuntos
Vírus da Influenza A/patogenicidade , Influenza Aviária/virologia , Influenza Humana/virologia , Substituição de Aminoácidos , Animais , China , Patos/virologia , Humanos , Vírus da Influenza A/genética , Filogenia , Vírus Reordenados , Análise de Sequência , Vietnã
14.
J Vet Sci ; 20(3): e27, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161745

RESUMO

In 2016, novel H5N6 highly pathogenic avian influenza virus emerged in Korea. During the outbreak, the virus caused the largest culling, especially in brown chicken lines. We determined the pathogenicity and transmissibility of the virus in 2 white chicken lines of the specific pathogen-free chickens, broilers and brown chicken line of Korean native chicken (KNC). A KNC had a longer virus shedding period and longer mean death time than others. Our study showed that this characteristic in the KNC might have contributed to a farm-to-farm transmission of the brown chicken farms.


Assuntos
Vírus da Influenza A/patogenicidade , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Animais , Cruzamento , Galinhas/virologia , Influenza Aviária/transmissão , Doenças das Aves Domésticas/transmissão , República da Coreia , Virulência
15.
Transbound Emerg Dis ; 66(5): 2188-2195, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31241237

RESUMO

The 1918 Spanish flu virus has claimed more than 50 million lives. However, the mechanism of its high pathogenicity remains elusive; and the origin of the virus is controversial. The matrix (M) segment regulates the replication of influenza A virus, thereby affecting its virulence and pathogenicity. This study found that the M segment of the Spanish flu virus is a recombinant chimera originating from avian influenza virus and human influenza virus. The unique mosaic M segment might confer the virus high replication capacity, showing that the recombination might play an important role in inducing high pathogenicity of the virus. In addition, this study also suggested that the NA and NS segments of the virus were generated by reassortment between mammalian and avian viruses. Direct phylogenetic evidence was also provided for its avian origin.


Assuntos
Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/virologia , Vírus Reordenados/genética , Animais , Galinhas , Humanos , Vírus da Influenza A/patogenicidade , Influenza Pandêmica, 1918-1919 , Filogenia , Vírus Reordenados/patogenicidade
16.
BMC Infect Dis ; 19(1): 458, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117981

RESUMO

BACKGROUND: Since 2008, avian influenza surveillance in poultry-related environments has been conducted annually in China. Samples have been collected from environments including live poultry markets, wild bird habitats, slaughterhouses, and poultry farms. Multiple subtypes of avian influenza virus have been identified based on environmental surveillance, and an H1N8 virus was isolated from the drinking water of a live poultry market. METHODS: Virus isolation was performed by inoculating influenza A-positive specimens into embryonated chicken eggs. Next-generation sequencing was used for whole-genome sequencing. A solid-phase binding assay was performed to test the virus receptor binding specificity. Trypsin dependence plaque formation assays and intravenous pathogenicity index tests were used to evaluate virus pathogenicity in vitro and in vivo, respectively. Different cell lines were chosen for comparison of virus replication capacity. RESULTS: According to the phylogenetic trees, the whole gene segments of the virus named A/Environment/Fujian/85144/2014(H1N8) were of Eurasian lineage. The HA, NA, PB1, and M genes showed the highest homology with those of H1N8 or H1N2 subtype viruses isolated from local domestic ducks, while the PB2, PA, NP and NS genes showed high similarity with the genes of H7N9 viruses detected in 2017 and 2018 in the same province. This virus presented an avian receptor binding preference. The plaque formation assay showed that it was a trypsin-dependent virus. The intravenous pathogenicity index (IVPI) in chickens was 0.02. The growth kinetics of the A/Environment/Fujian/85144/2014(H1N8) virus in different cell lines were similar to those of a human-origin virus, A/Brisbane/59/2007(H1N1), but lower than those of the control avian-origin and swine-origin viruses. CONCLUSIONS: The H1N8 virus was identified in avian influenza-related environments in China for the first time and may have served as a gene carrier involved in the evolution of the H7N9 virus in poultry. This work further emphasizes the importance of avian influenza virus surveillance, especially in live poultry markets (LPMs). Active surveillance of avian influenza in LPMs is a major pillar supporting avian influenza control and response.


Assuntos
Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Animais , Linhagem Celular , Embrião de Galinha , Galinhas , China , Patos , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Filogenia , Aves Domésticas/virologia , Tripsina/genética , Tripsina/metabolismo , Sequenciamento Completo do Genoma
17.
Nat Microbiol ; 4(8): 1316-1327, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31110357

RESUMO

The upper respiratory tract is continuously exposed to a vast array of potentially pathogenic viruses and bacteria. Influenza A virus (IAV) has particular synergism with the commensal bacterium Streptococcus pneumoniae in this niche, and co-infection exacerbates pathogenicity and causes significant mortality. However, it is not known whether this synergism is associated with a direct interaction between the two pathogens. We have previously reported that co-administration of a whole-inactivated IAV vaccine (γ-Flu) with a whole-inactivated pneumococcal vaccine (γ-PN) enhances pneumococcal-specific responses. In this study, we show that mucosal co-administration of γ-Flu and γ-PN similarly augments IAV-specific immunity, particularly tissue-resident memory cell responses in the lung. In addition, our in vitro analysis revealed that S. pneumoniae directly interacts with both γ-Flu and with live IAV, facilitating increased uptake by macrophages as well as increased infection of epithelial cells by IAV. These observations provide an additional explanation for the synergistic pathogenicity of IAV and S. pneumoniae, as well as heralding the prospect of exploiting the phenomenon to develop better vaccine strategies for both pathogens.


Assuntos
Imunidade , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Vacinas Pneumocócicas/imunologia , Animais , Coinfecção/imunologia , Coinfecção/prevenção & controle , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Células Epiteliais , Feminino , Humanos , Vírus da Influenza A/patogenicidade , Vacinas contra Influenza/administração & dosagem , Pulmão/imunologia , Macrófagos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/patogenicidade , Linfócitos T/imunologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31142047

RESUMO

The factors affecting the transmission and geographic translocation of avian influenza viruses (AIVs) within wild migratory bird populations remain inadequately understood. In a previous study, we found that environmental transmission had little impact on AIV translocation in a model of a single migratory bird population. In order to simulate virus transmission and translocation more realistically, here we expanded this model system to include two migratory bird flocks. We simulated AIV transmission and translocation while varying four core properties: 1) Contact transmission rate; 2) infection recovery rate; 3) infection-induced mortality rate; and 4) migration recovery rate; and three environmental transmission properties: 1) Virion persistence; 2) exposure rate; and 3) re-scaled environmental infectiousness; as well as the time lag in the migration schedule of the two flocks. We found that environmental exposure rate had a significant impact on virus translocation in the two-flock model. Further, certain epidemiological features (i.e., low infection recovery rate, low mortality rate, and high migration transmission rate) in both flocks strongly affected the likelihood of virus translocation. Our results further identified the pathobiological features supporting AIV intercontinental dissemination risk.


Assuntos
Aves/virologia , Vírus da Influenza A/patogenicidade , Influenza Aviária/transmissão , Migração Animal , Animais , Animais Selvagens , Influenza Aviária/virologia
20.
Nat Commun ; 10(1): 1629, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967547

RESUMO

Influenza A virus has an eight-partite RNA genome that during viral assembly forms a complex containing one copy of each RNA. Genome assembly is a selective process driven by RNA-RNA interactions and is hypothesized to lead to discrete punctate structures scattered through the cytosol. Here, we show that contrary to the accepted view, formation of these structures precedes RNA-RNA interactions among distinct viral ribonucleoproteins (vRNPs), as they assemble in cells expressing only one vRNP type. We demonstrate that these viral inclusions display characteristics of liquid organelles, segregating from the cytosol without a delimitating membrane, dynamically exchanging material and adapting fast to environmental changes. We provide evidence that viral inclusions develop close to endoplasmic reticulum (ER) exit sites, depend on continuous ER-Golgi vesicular cycling and do not promote escape to interferon response. We propose that viral inclusions segregate vRNPs from the cytosol and facilitate selected RNA-RNA interactions in a liquid environment.


Assuntos
Retículo Endoplasmático/virologia , Vírus da Influenza A/fisiologia , Influenza Humana/patologia , Ribonucleoproteínas/metabolismo , Proteínas Virais/metabolismo , Montagem de Vírus , Células A549 , Animais , Citosol/metabolismo , Citosol/virologia , Cães , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Complexo de Golgi/virologia , Células HEK293 , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A/patogenicidade , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Ligação Proteica , RNA Viral/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
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