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1.
Arch Virol ; 165(1): 55-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31696308

RESUMO

A swine influenza survey was conducted between 2003 and 2015 in Germany. During this period, 8122 snout swabs or other respiratory specimens from pigs of 5178 herds, mainly from Germany, were investigated for the presence of swine influenza A virus (S-IAV). In total, 1310 S-IAV isolates were collected. Of this collection, the complete genome of 267 H1N2 S-IAV isolates was sequenced and phylogenetically analyzed. The data demonstrate the incursion of human-like swine H1N2 viruses (Gent/1999-like) in 2000 and prevalent circulation until 2010. From 2008 onward, a sustained and broad change of the genetic constellation of the swine H1N2 subtype commenced. The Gent/1999-like swine H1N2 viruses ceased and several new swine H1N2 reassortants emerged and became prevalent in Germany. Of these, the upsurge of the Diepholz/2008-like, Emmelsbuell/2009-like and Papenburg/2010-like viruses is notable. The data reveal the importance of reassortment events in S-IAV evolution. The strong circulation of S-IAV of different lineages in the swine population throughout the year underlines that pigs are important reservoir hosts.


Assuntos
Vírus da Influenza A Subtipo H1N2/classificação , Infecções por Orthomyxoviridae/epidemiologia , Vírus Reordenados/classificação , Análise de Sequência de RNA/métodos , Animais , Alemanha/epidemiologia , Humanos , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H1N2/isolamento & purificação , Infecções por Orthomyxoviridae/virologia , Filogenia , Prevalência , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Suínos
2.
Int J Nanomedicine ; 14: 8469-8481, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695375

RESUMO

Background: A pandemic influenza viral strain, influenza A/California/07/2009 (pdmH1N1), has been considered to be a potential issue that needs to be controlled to avoid the seasonal emergence of mutated strains. Materials and methods: In this study, aptamer-antibody complementation was implemented on a multiwalled carbon nanotube-gold conjugated sensing surface with a dielectrode to detect pandemic pdmH1N1. Preliminary biomolecular and dielectrode surface analyses were performed by molecular and microscopic methods. A stable anti-pdmH1N1 aptamer sequence interacted with hemagglutinin (HA) and was compared with the antibody interaction. Both aptamer and antibody attachments on the surface as the basic molecule attained the saturation at nanomolar levels. Results: Aptamers were found to have higher affinity and electric response than antibodies against HA of pdmH1N1. Linear regression with aptamer-HA interaction displays sensitivity in the range of 10 fM, whereas antibody-HA interaction shows a 100-fold lower level (1 pM). When sandwich-based detection of aptamer-HA-antibody and antibody-HA-aptamer was performed, a higher response of current was observed in both cases. Moreover, the detection strategy with aptamer clearly discriminated the closely related HA of influenza B/Tokyo/53/99 and influenza A/Panama/2007/1999 (H3N2). Conclusion: The high performance of the abovementioned detection methods was supported by the apparent specificity and reproducibility by the demonstrated sensing system.


Assuntos
Anticorpos Antivirais/imunologia , Aptâmeros de Nucleotídeos/química , Ouro/química , Vírus da Influenza A Subtipo H1N1/imunologia , Nanotubos de Carbono/química , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Pandemias , Suínos/virologia , Animais , Proteínas do Sistema Complemento/metabolismo , Eletrodos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Limite de Detecção , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Transdução Genética
3.
Emerg Microbes Infect ; 8(1): 1535-1545, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661383

RESUMO

Influenza A virus infections occur in different species, causing mild to severe respiratory symptoms that lead to a heavy disease burden. Eurasian avian-like swine influenza A(H1N1) viruses (EAS-H1N1) are predominant in pigs and occasionally infect humans. An influenza A(H1N1) virus was isolated from a boy who was suffering from fever and headache and designated as A/Tianjin-baodi/1606/2018(H1N1). Full-genome sequencing and phylogenetic analysis revealed that A/Tianjin-baodi/1606/2018(H1N1) is a novel reassortant EAS-H1N1 containing gene segments from EAS-H1N1 (HA and NA), classical swine H1N1(NS) and A(H1N1)pdm09(PB2, PB2, PA, NP and M) viruses. The isolation and analysis of A/Tianjin-baodi/1606/2018(H1) provide further evidence that EAS-H1N1 poses a threat to human health and greater attention should be paid to surveillance of influenza virus infection in pigs and humans.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/isolamento & purificação , Doenças dos Suínos/virologia , Animais , Criança , China , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Influenza Aviária/virologia , Masculino , Infecções por Orthomyxoviridae/virologia , Filogenia , Aves Domésticas , Doenças das Aves Domésticas/virologia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Suínos
4.
Nat Commun ; 10(1): 4107, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511530

RESUMO

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is essential for fighting infection, a balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms affect survival in influenza infection. Circadian control of influenza infection is mediated by enhanced inflammation as proven by increased cellularity in bronchoalveolar lavage (BAL), pulmonary transcriptomic profile and histology and is not attributable to viral burden. Better survival is associated with a time dependent preponderance of NK and NKT cells and lower proportion of inflammatory monocytes in the lung. Further, using a series of genetic mouse mutants, we elucidate cellular mechanisms underlying circadian gating of influenza infection.


Assuntos
Ritmo Circadiano/fisiologia , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/fisiopatologia , Pneumonia/complicações , Pneumonia/fisiopatologia , Fatores de Transcrição ARNTL/deficiência , Fatores de Transcrição ARNTL/metabolismo , Animais , Antígenos Ly , Feminino , Vírus da Influenza A/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/metabolismo , Células Mieloides/metabolismo , Células T Matadoras Naturais/imunologia , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/virologia , Fenótipo , Pneumonia/virologia , Fatores de Tempo , Transcriptoma/genética , Replicação Viral
5.
Vet Res ; 50(1): 63, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533860

RESUMO

Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.


Assuntos
Doenças Respiratórias/veterinária , Doenças dos Suínos/epidemiologia , Animais , Betacoronavirus 1/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Vírus da Influenza A/isolamento & purificação , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Síndrome Respiratória e Reprodutiva Suína/epidemiologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Prevalência , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/virologia , Respirovirus/isolamento & purificação , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/veterinária , Infecções por Respirovirus/virologia , Sus scrofa , Suínos , Doenças dos Suínos/virologia , Thogotovirus/isolamento & purificação , Estados Unidos/epidemiologia
6.
Emerg Microbes Infect ; 8(1): 1324-1336, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31503518

RESUMO

Avian influenza A viruses (AIV) of the H7 subtype continue to evolve posing a pandemic threat. However, molecular markers of H7N7 AIV pathogenicity and transmission in mammals remain poorly understood. In this study, we performed a systematic in vitro and in vivo analysis by comparing an H7N7 highly pathogenic AIV and its ferret adapted variant. Passaging an H7N7 AIV in ferrets led to six mutations in genes encoding the viral polymerase complex and the viral surface proteins. Here, we show that mutations in the H7 hemagglutinin gene cause increased pathogenicity in mice. Contact transmission between guinea pigs required additional mutations in the gene encoding the polymerase subunit PB1. Thus, particular vigilance is required with respect to HA and PB1 mutations as predictive molecular markers to assess the pandemic risk posed by emerging H7 avian influenza viruses.


Assuntos
Transmissão de Doença Infecciosa , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H7N7/patogenicidade , Proteínas Mutantes/genética , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Proteínas Virais/genética , Animais , Modelos Animais de Doenças , Furões , Cobaias , Vírus da Influenza A Subtipo H7N7/genética , Infecções por Orthomyxoviridae/patologia , Inoculações Seriadas , Fatores de Virulência/genética
7.
BMC Infect Dis ; 19(1): 762, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477028

RESUMO

BACKGROUND: Avian influenza A (H5N6) virus poses a great threat to the human health since it is capable to cross the species barrier and infect humans. Although human infections are believed to largely originate from poultry contaminations, the transmissibility is unclear and only limited information was available on poultry environment contaminations, especially in Fujian Province. METHODS: A total of 4901 environmental samples were collected and tested for Avian Influenza Virus (AIV) from six cities in Fujian Province through the Fujian Influenza Surveillance System from 2013 to 2017. Two patient-related samples were taken from Fujian's first confirmed H5N6 human case and his backyard chicken feces in 2017. Chi-square test or Fisher's exact probability test was used to compare the AIV and the viral subtype positive rates among samples from different Surveillance cities, surveillance sites, sample types, and seasons. Phylogenetic tree analysis and molecular analysis were conducted to track the viral transmission route of the human infection and to map out the evolutions of H5N6 in Fujian. RESULTS: The overall positive rate of the H5 subtype AIVs was 4.24% (208/4903). There were distinctive differences (p < 0.05) in the positive rates in samples from different cities, sample sites, sample types and seasons. The viruses from the patient and his backyard chicken feces shared high homologies (99.9-100%) in all the eight gene segments. Phylogenetic trees also showed that these two H5N6 viruses were closely related to each other, and were classified into the same genetic clade 2.3.4.4 with another six H5N6 isolates from the environmental samples. The patient's H5N6 virus carried genes from H6N6, H5N8 and H5N6 viruses originated from different areas. The R294K or N294S substitution was not detected in the neuraminidase (NA). The S31 N substitution in the matrix2 (M2) gene was detected but only in one strain from the environmental samples. CONCLUSIONS: The H5 subtype of AIVs has started circulating in the poultry environments in Fujian Province. The patient's viral strain originated from the chicken feces in his backyard. Genetic reassortment in H5N6 viruses in Fujian Province was indicated. The H5N6 viruses currently circulating in Fujian Province were still commonly sensitive to Oseltamivir and Zanamivir, but the resistance against Amantadine has emerged.


Assuntos
Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Aves Domésticas/virologia , Animais , Embrião de Galinha , Galinhas/virologia , China/epidemiologia , Patos/virologia , Meio Ambiente , Microbiologia Ambiental , Genes Virais , Abrigo para Animais/normas , Humanos , Vírus da Influenza A/genética , Influenza Aviária/diagnóstico , Influenza Aviária/epidemiologia , Tipagem Molecular , Infecções por Orthomyxoviridae/diagnóstico , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/transmissão , Filogenia , Doenças das Aves Domésticas/diagnóstico , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/virologia , Fatores de Risco
8.
Int J Infect Dis ; 88: 113-119, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401200

RESUMO

Here we review evidence for influenza A viruses (IAVs) moving from swine, avian, feline, equine, and canine species to infect humans. We review case reports, sero-epidemiological, archeo-epidemiological, environmental, and historical studies and consider trends in livestock farming. Although this focused review is not systematic, the aggregated data point to industrialized swine farming as the most likely source of future pandemic viruses, yet IAV surveillance on such farms is remarkably sparse. We recommend increased biosafety and biosecurity training for farm administrators and swine workers with One Health-oriented virus surveillance throughout industrialized farming and meat production lines. Collaborative partnerships with human medical researchers could aid in efforts to mitigate emerging virus threats by offering new surveillance and diagnostic technologies to livestock farming industries.


Assuntos
Vírus da Influenza A/fisiologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Animais , Aves , Gatos , Cães , Cavalos , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/transmissão , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Suínos
9.
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
10.
Infect Immun ; 87(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31383747

RESUMO

Postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Proteínas Hemolisinas/antagonistas & inibidores , Linezolida/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções por Orthomyxoviridae/complicações , Pneumonia Estafilocócica/tratamento farmacológico , Animais , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Feminino , Expressão Gênica , Gentamicinas/farmacologia , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , L-Lactato Desidrogenase/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Masculino , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Plasmídeos/química , Plasmídeos/metabolismo , Pneumonia Estafilocócica/complicações , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/mortalidade , Análise de Sobrevida , Vancomicina/farmacologia
11.
PLoS Comput Biol ; 15(8): e1007294, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31425503

RESUMO

The strength and breadth of an individual's antibody repertoire is an important predictor of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but have not previously been included in mathematical models of antibody landscapes, including: titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting a role for a mechanism describing diminishing antibody boosting with repeated exposures. Although there was considerable uncertainty in our estimates of antibody waning parameters, our results suggest that both short and long term waning were present and would be identifiable with a larger set of experiments. These results highlight the potential use of repeat exposure animal models in revealing short-term, strain-specific immune dynamics of influenza.


Assuntos
Anticorpos Antivirais/sangue , Furões/imunologia , Vacinas contra Influenza/administração & dosagem , Modelos Imunológicos , Infecções por Orthomyxoviridae/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Biologia Computacional , Reações Cruzadas , Modelos Animais de Doenças , Humanos , Imunização Secundária , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Cinética , Infecções por Orthomyxoviridae/virologia , Vacinas de Produtos Inativados/administração & dosagem
12.
PLoS Pathog ; 15(8): e1007989, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31412088

RESUMO

Defining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of inflammatory factors in the infected lung. Blocking CD70-CD27 signals to reduce CD4 T cell IL-2 production tempers the inflammation induced by wild-type memory CD4 T cells and improves the outcome of IAV infection in vaccinated mice. Finally, we show that IL-2 administration drives rapid and extremely potent lung inflammation involving NK cells, which can synergize with sublethal IAV infection to promote acute death. These results suggest that IL-2 production is not necessarily an indicator of protective CD4 T cells, and that the lung environment is particularly sensitive to IL-2-induced inflammation during viral infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica/imunologia , Vírus da Influenza A/imunologia , Interleucina-2/metabolismo , Infecções por Orthomyxoviridae/imunologia , Pneumonia/imunologia , Animais , Feminino , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/virologia , Pneumonia/metabolismo , Pneumonia/virologia
13.
Emerg Microbes Infect ; 8(1): 989-999, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31267843

RESUMO

It has recently been proposed that the Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) is one of the most likely zoonotic viruses to cause the next influenza pandemic. Two main genotypes EA H1N1 viruses have been recognized to be infected humans in China. Our study finds that one of the genotypes JS1-like viruses are avirulent in mice. However, the other are HuN-like viruses and are virulent in mice. The molecular mechanism underlying this difference shows that the NP gene determines the virulence of the EA H1N1 viruses in mice. In addition, a single substitution, Q357K, in the NP protein of the EA H1N1 viruses alters the virulence phenotype. This substitution is a typical human signature marker, which is prevalent in human viruses but rarely detected in avian influenza viruses. The NP-Q357K substitution is readily to be occurred when avian influenza viruses circulate in pigs, and may facilitate their infection of humans and allow viruses also carrying NP-357K to circulate in humans. Our study demonstrates that the substitution Q357K in the NP protein plays a key role in the virulence phenotype of EA H1N1 SIVs, and provides important information for evaluating the pandemic risk of field influenza strains.


Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , Mutação de Sentido Incorreto , Infecções por Orthomyxoviridae/veterinária , Proteínas de Ligação a RNA/genética , Doenças dos Suínos/virologia , Proteínas do Core Viral/genética , Animais , China , Feminino , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/virologia , Filogenia , Proteínas de Ligação a RNA/metabolismo , Suínos , Proteínas do Core Viral/metabolismo , Virulência , Replicação Viral
14.
Biosens Bioelectron ; 141: 111476, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31272058

RESUMO

The ability of influenza viruses to rapidly evolve has caused significant challenges in viral surveillance, diagnosis, and therapeutic development. Molecular sequencing methods, though powerful tools for monitoring influenza evolution at the genetic level, are not able to fully characterize the antigenic properties of influenza viruses. Understanding influenza virus antigenicity is critical to vaccine development and disease prevention. Traditional immunoassays which have been widely used for evaluating influenza antigenicity have limited throughput. To alleviate these problems, new bioanalytical tools to investigate influenza antigenicity by measuring antibody-antigen binding are an active area of research. Herein, we review immunosensor technologies from the aspects of various sensing principles, while highlighting recent developments in multiplex, label-free detection strategies. Highlighted technologies include electrochemical immunosensors relying on impedimetric detection; these demonstrate simple design and cost effectiveness for mass production. Antibody arrays implemented on an optical interferometric sensor system allow systematic characterization of influenza antigenicity. Quartz microbalance immunosensors are highly sensitive but have yet to be explored for multiplex sensing. Immunosensors made on lateral flow strips have shown promise in rapid diagnosis of influenza subtypes. We anticipate that these and other technologies discussed in the review will facilitate advances in the study of influenza, and other viral pathogens.


Assuntos
Técnicas Biossensoriais/métodos , Influenza Humana/diagnóstico , Orthomyxoviridae/isolamento & purificação , Animais , Antígenos Virais/análise , Antígenos Virais/imunologia , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Influenza Humana/imunologia , Influenza Humana/virologia , Influenzavirus A/imunologia , Influenzavirus A/isolamento & purificação , Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/diagnóstico , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia
15.
J Microbiol Biotechnol ; 29(7): 1155-1164, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31280524

RESUMO

Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 logfold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-HDMSE) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, HIF-1α, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including HIF-1α signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.


Assuntos
Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Líquens/química , Infecções por Orthomyxoviridae/metabolismo , Animais , Antivirais/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cães , Líquens/metabolismo , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/virologia , Proteômica , RNA Mensageiro/metabolismo , República da Coreia , Transdução de Sinais/efeitos dos fármacos , Proteínas Virais/genética
16.
Emerg Microbes Infect ; 8(1): 1017-1026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31287780

RESUMO

Host switch events of influenza A viruses (IAVs) continuously pose a zoonotic threat to humans. In 2013, swine-origin H1N1 IAVs emerged in dogs soon after they were detected in swine in the Guangxi province of China. This host switch was followed by multiple reassortment events between these H1N1 and previously circulating H3N2 canine IAVs (IAVs-C) in dogs. To evaluate the phenotype of these newly identified viruses, we characterized three swine-origin H1N1 IAVs-C and one reassortant H1N1 IAV-C. We found that H1N1 IAVs-C predominantly bound to human-type receptors, efficiently transmitted via direct contact in guinea pigs and replicated in human lung cells. Moreover, the swine-origin H1N1 IAVs-C were lethal in mice and were transmissible by respiratory droplets in guinea pigs. Importantly, sporadic human infections with these viruses have been detected, and preexisting immunity in humans might not be sufficient to prevent infections with these new viruses. Our results show the potential of H1N1 IAVs-C to infect and transmit in humans, suggesting that these viruses should be closely monitored in the future.


Assuntos
Doenças do Cão/virologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , China , Doenças do Cão/mortalidade , Cães , Feminino , Cobaias , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/mortalidade , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/virologia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/patogenicidade , Suínos , Doenças dos Suínos/mortalidade , Virulência
17.
PLoS Pathog ; 15(7): e1007919, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31265471

RESUMO

Avian influenza virus H9N2 has been endemic in birds in the Middle East, in particular in Egypt with multiple cases of human infections since 1998. Despite concerns about the pandemic threat posed by H9N2, little is known about the biological properties of H9N2 in this epicentre of infection. Here, we investigated the evolutionary dynamics of H9N2 in the Middle East and identified phylogeny-associated PB2 mutations that acted cooperatively to increase H9N2 replication/transcription in human cells. The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence. These mutations clustered on a solvent-exposed region in the PB2-627 domain in proximity to potential interfaces with host factors. These PB2 mutations have been found at high prevalence during evolution of H9N2 in the field, indicating that they have provided a selective advantage for viral adaptation to infect poultry. Therefore, continuous prevalence of H9N2 virus in the Middle East has generated a far more fit or optimized replication phenotype, leading to an expanded viral host range, including to mammals, which may pose public health risks beyond the current outbreaks.


Assuntos
Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/patogenicidade , Influenza Humana/virologia , Mutação , RNA Replicase/genética , Proteínas Virais/genética , Animais , Evolução Molecular , Feminino , Células HEK293 , Especificidade de Hospedeiro/genética , Humanos , Vírus da Influenza A Subtipo H9N2/fisiologia , Influenza Humana/epidemiologia , Mamíferos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Oriente Médio/epidemiologia , Modelos Moleculares , Infecções por Orthomyxoviridae/virologia , Filogenia , RNA Replicase/química , RNA Replicase/metabolismo , Vírus Reordenados/genética , Vírus Reordenados/patogenicidade , Vírus Reordenados/fisiologia , Proteínas Virais/química , Proteínas Virais/metabolismo , Virulência/genética , Replicação Viral/genética , Zoonoses/virologia
19.
Nat Commun ; 10(1): 2887, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253760

RESUMO

Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4+ effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology during Toxoplasma gondii infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.


Assuntos
Candidíase/metabolismo , Interferon Tipo I/metabolismo , Interferon gama/metabolismo , Melioidose/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Animais , Burkholderia pseudomallei , Candida albicans , Candidíase/imunologia , Candidíase/microbiologia , Regulação da Expressão Gênica/imunologia , Vírus da Influenza A Subtipo H3N2 , Interferon Tipo I/sangue , Interferon Tipo I/genética , Interferon gama/sangue , Interferon gama/genética , Pulmão , Melioidose/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Receptor de Interferon alfa e beta , Receptores de Interferon , Infecções por Vírus Respiratório Sincicial/imunologia
20.
Nat Commun ; 10(1): 2846, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253788

RESUMO

The magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)366-374 presentation, while cross-presentation is optimal for acid polymerase (PA)224-233 presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.


Assuntos
Apresentação do Antígeno/fisiologia , Epitopos de Linfócito T/fisiologia , Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Linfócitos T Citotóxicos/fisiologia , Animais , Linhagem Celular , Epitopos de Linfócito T/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos , Análise Multivariada , Infecções por Orthomyxoviridae/virologia
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