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1.
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
2.
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
3.
Acta Virol ; 63(2): 195-202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230448

RESUMO

The 1918 "Spanish" pandemic is the earliest known influenza H1N1 virus. Since then H1N1 viruses circulated between humans and animals continuously. With the increased amount of samples of H1N1 viruses and technology development, researchers have been studying how the viruses evolved. Here, we analyzed HA and NA genes of H1N1 viruses from three aspects: host distribution, geographical distribution and phylogenetic analysis. The data showed hosts were predominantly human, swine and poultry, and other hosts were mainly cat, ferret, wild bear, canine, cheetah and seal. In terms of geographical distribution, the North America and Eurasia were the main H1N1 influenza pandemic areas. Of them, the United States, China, Japan, Canada, the United Kingdom, India and Singapore were the most affected. The phylogenetic analysis of surface genes of influenza H1N1 viruses from 1918 to 2017 worldwide revealed the distribution of all avian influenza viruses (AIVs) showed a clear geographical difference, mainly concentrated in Eurasia and America. American and Eurasian swine viruses might be the ancestors of the 2009 pandemic virus' HA and NA genes. Swine influenza viruses played an important role in the spread of influenza viruses across species. To our knowledge, this is the first large-scale phylogenetic analysis of HA and NA genes of influenza H1N1 viruses worldwide until now. Our findings further emphasize the importance of surveillance of the genetic diversity of influenza H1N1 viruses in different hosts and raised more concerns about the long-time monitoring. Keywords: influenza H1N1 viruses; HA genes; NA genes; phylogenetic analysis; evolution.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Filogenia , Animais , Gatos , China , Cães , Interações Hospedeiro-Patógeno , Humanos , Índia , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Suínos
4.
Acta Virol ; 63(1): 121-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30879322

RESUMO

The H8 subtype viruses are rarely isolated from wild ducks. Shanghai is one of the important wintering or stopover sites on the East Asia-Australia Migration Flyway. An influenza virus, subtype H8N4, was firstly isolated from a common teal (Anas crecca) in Shanghai during 2017-2018 in this study. To clarify the genetic characteristics of the H8N4 virus, the whole genome sequences were analyzed. Phylogenetic analysis of the hemagglutinin and neuraminidase genes showed that they shared highest nucleotide identity (99.19%-99.64%) with the Japan duck-origin H8N4 virus collected in 2016 (A/duck/Aichi/231003/2016) and belonged to the Eurasian-like avian lineage. Six other genes of the H8N4 isolated virus were all highly similar to the corresponding genes of a wide range of AIV subtypes including H9N2, H5N7, H3N8, H1N2, H4N6 and H1N1. The results indicated that the H8N4 virus was a multiple reassortant virus. The study emphasized that the continuous surveillance of influenza virus in wild birds should be strengthened. Keywords: avian influenza virus; H8N4; phylogenetic analysis; Shanghai.


Assuntos
Vírus da Hepatite A , Influenza Aviária , Animais , Aves , China , Patos , Vírus da Hepatite A/classificação , Vírus da Hepatite A/genética , Vírus da Hepatite A/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N8/classificação , Vírus da Influenza A Subtipo H3N8/genética , Vírus da Influenza A Subtipo H3N8/isolamento & purificação , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária/virologia , Filogenia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação
5.
Arch Virol ; 164(2): 457-472, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30415389

RESUMO

Surveillance studies of influenza A virus of swine (IAV-S) have accumulated information regarding IAVs-S circulating in Thailand, but how IAVs-S evolve within a farm remains unclear. In the present study, we isolated 82 A(H1N1)pdm09 and 87 H3N2 viruses from four farms from 2011 through 2017. We then phylogenetically and antigenically analyzed the isolates to elucidate their evolution within each farm. Phylogenetic analysis demonstrated multiple introductions of A(H1N1)pdm09 viruses that resembled epidemic A(H1N1)pdm09 strains in humans in Thailand, and they reassorted with H3N2 viruses as well as other A(H1N1)pdm09 viruses. Antigenic analysis revealed that the viruses had acquired antigenic diversity either by accumulating substitutions in the hemagglutinin protein or through the introduction of IAV-S strains with different antigenicity. Our results, obtained through continuous longitudinal surveillance, revealed that IAV-S can be maintained on a pig farm over several years through the generation of antigenic diversity due to the accumulation of mutations, introduction of new strains, and reassortment events.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , Variação Antigênica , Variação Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Estudos Longitudinais , Infecções por Orthomyxoviridae/virologia , Filogenia , Suínos , Tailândia
6.
Syst Biol ; 68(2): 358-364, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945220

RESUMO

Rapidly evolving pathogens, such as viruses and bacteria, accumulate genetic change at a similar timescale over which their epidemiological processes occur, such that, it is possible to make inferences about their infectious spread using phylogenetic time-trees. For this purpose it is necessary to choose a phylodynamic model. However, the resulting inferences are contingent on whether the model adequately describes key features of the data. Model adequacy methods allow formal rejection of a model if it cannot generate the main features of the data. We present TreeModelAdequacy, a package for the popular BEAST2 software that allows assessing the adequacy of phylodynamic models. We illustrate its utility by analyzing phylogenetic trees from two viral outbreaks of Ebola and H1N1 influenza. The main features of the Ebola data were adequately described by the coalescent exponential-growth model, whereas the H1N1 influenza data were best described by the birth-death susceptible-infected-recovered model.


Assuntos
Simulação por Computador , Ebolavirus/classificação , Ebolavirus/genética , Genoma Viral/genética , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Filogenia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Software
7.
Virus Res ; 259: 38-45, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30336188

RESUMO

In 2015, the influenza virus A/H1N1/pdm09 strain outbreak became prevalent throughout the different provinces of Iran. There are relatively limited complete genetic sequences available for this virus from Asian countries. Diagnosis and virological surveillance of influenza is essential for detecting novel genetic variants causing epidemic potential. This study describes the genetic properties of HA genome of influenza A/H1N1 pdm09 viruses circulating in Iran during the 2015/2016 season. In order to investigate the genetic pattern of influenza A/H1N1 pdm09, a total of 1758 nasopharyngeal swabs were screened by real-time RT-PCR. Of those, 510 cases were found to be positive for A/H1N1/pdm09 virus. Evolution of the approximately 100 positive specimens with high virus load was conducted via genomic phylogeny. Phylogenetic analysis of the HA genes of the A/H1N1pdm09 viruses revealed the circulation of clade 6B1, characterized by amino acid substitutions S84N, S162N and I216T, where position 162 became glycosylated. The N-glycosylation of HA protein is post or co-translational modification that affect the evolution of influenza viruses. For influenza A(H1N1) pdm09 viruses, we found more mutations in the antigenic sites than in the stem region. The results of this study confirmed the necessity of constant regular antigenic and molecular surveillance of circulating seasonal influenza viruses.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Substituição de Aminoácidos , Animais , Linhagem Celular , Variação Genética , Genótipo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Irã (Geográfico)/epidemiologia , Modelos Moleculares , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Filogenia , Prevalência , Conformação Proteica , Estações do Ano
8.
Antiviral Res ; 160: 1-9, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30315875

RESUMO

INTRODUCTION: A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013-2014 influenza season, despite cord blood transplantation and antiviral treatments. METHODS: Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens. RESULTS: The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status. CONCLUSIONS: Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.


Assuntos
Variação Genética , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/patologia , Influenza Humana/virologia , Imunodeficiência Combinada Severa/complicações , Antivirais/administração & dosagem , Antivirais/farmacologia , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Farmacorresistência Viral , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Mutação de Sentido Incorreto , Neuraminidase/genética , Oseltamivir/administração & dosagem , Oseltamivir/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Proteínas Virais/genética , Zanamivir/administração & dosagem
10.
PLoS One ; 13(9): e0203995, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30265699

RESUMO

INTRODUCTION: The establishment of the influenza sentinel surveillance system in Kinshasa, Bas Congo, Maniema, Katanga, and Kasai Provinces allowed generation of important data on the molecular epidemiology of human influenza viruses circulating in the Democratic Republic of Congo (DRC). However, some challenges still exist, including the need for extending the influenza surveillance to more provinces. This study describes the pattern of influenza virus circulating in DRC during 2015. METHODOLOGY: Nasopharyngeal swabs were collected from January to December 2015 from outpatients with influenza-like illness (ILI) and in all hospitalized patients with Severe Acute Respiratory Infection (SARI). Molecular analysis was done to determine influenza type and subtype at the National Reference Laboratory (NRL) in Kinshasa using real time reverse transcription-polymerase chain reaction (rRT-PCR). Analysis of antiviral resistance by enzyme inhibition assay and nucleotide sequencing was performed by the Collaborating center in the USA (CDC, Atlanta). RESULTS: Out of 2,376 nasopharyngeal swabs collected from patients, 218 (9.1%) were positive for influenza virus. Among the positive samples, 149 were characterized as influenza virus type A (Flu A), 67 as type B (Flu B) and 2 mixed infections (Flu A and B). Flu A subtypes detected were H3N2 and H1N1. The Yamagata strain of Flu B was detected among patients in the country. Individuals aged between 5 and 14 years accounted for the largest age group affected by influenza virus. All influenza viruses detected were found to be sensitive to antiviral drugs such as oseltamivar, zanamivir, peramivir and laninamivar. CONCLUSION: The present study documented the possible involvement of both circulation of Flu A and B viruses in human respiratory infection in certain DRC provinces during 2015. This study emphasises the need to extend the influenza surveillance to other provinces for a better understanding of the epidemiology of influenza in DRC. It is envisioned that such a system would lead to improved disease control and patient management.


Assuntos
Influenza Humana/epidemiologia , Influenza Humana/virologia , Adolescente , Adulto , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Farmacorresistência Viral/genética , Feminino , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Vírus da Influenza B/classificação , Vírus da Influenza B/efeitos dos fármacos , Vírus da Influenza B/genética , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Vigilância de Evento Sentinela , Adulto Jovem
11.
J Virol ; 92(24)2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30258006

RESUMO

The H1N1 influenza virus responsible for the most recent pandemic in 2009 (H1N1pdm) has spread to swine populations worldwide while it replaced the previous seasonal H1N1 virus in humans. In France, surveillance of swine influenza A viruses in pig herds with respiratory outbreaks led to the detection of 44 H1N1pdm strains between 2009 and 2017, regardless of the season, and findings were not correlated with pig density. From these isolates, 17 whole-genome sequences were obtained, as were 6 additional hemagglutinin (HA)/neuraminidase (NA) sequences, in order to perform spatial and temporal analyses of genetic diversity and to compare evolutionary patterns of H1N1pdm in pigs to patterns for human strains. Following mutation accumulation and fixation over time, phylogenetic analyses revealed for the first time the divergence of a swine-specific genogroup within the H1N1pdm lineage. The divergence is thought to have occurred around 2011, although this was demonstrated only through strains isolated in 2015 to 2016 in the southern half of France. To date, these H1N1pdm swine strains have not been related to any increased virulence in swine herds and have not exhibited any antigenic drift compared to seasonal human strains. However, further monitoring is encouraged, as diverging evolutionary patterns in these two species, i.e., swine and humans, may lead to the emergence of viruses with a potentially higher risk to both animal and human health.IMPORTANCE Pigs are a "mixing vessel" for influenza A viruses (IAVs) because of their ability to be infected by avian and human IAVs and their propensity to facilitate viral genomic reassortment events. Also, as IAVs may evolve differently in swine and humans, pigs can become a reservoir for old human strains against which the human population has become immunologically naive. Thus, viruses from the novel swine-specific H1N1pdm genogroup may continue to diverge from seasonal H1N1pdm strains and/or from other H1N1pdm viruses infecting pigs and lead to the emergence of viruses that would not be covered by human vaccines and/or swine vaccines based on antigens closely related to the original H1N1pdm virus. This discovery confirms the importance of encouraging swine IAV monitoring because H1N1pdm swine viruses could carry an increased risk to both human and swine health in the future as a whole H1N1pdm virus or gene provider in subsequent reassortant viruses.


Assuntos
Vírus da Influenza A Subtipo H1N1/classificação , Infecções por Orthomyxoviridae/epidemiologia , Doenças dos Suínos/virologia , Sequenciamento Completo do Genoma/métodos , Animais , Evolução Molecular , França/epidemiologia , Hemaglutininas/genética , Vírus da Influenza A Subtipo H1N1/genética , Neuraminidase/genética , Infecções por Orthomyxoviridae/virologia , Pandemias , Filogenia , Vigilância da População , Análise Espaço-Temporal , Suínos , Doenças dos Suínos/epidemiologia , Proteínas Virais/genética , Sequenciamento Completo do Genoma/veterinária
12.
ACS Appl Mater Interfaces ; 10(38): 31977-31987, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30184422

RESUMO

The development of a sensitive and rapid diagnostic test for early detection of infectious viruses is urgently required to defend against pandemic and infectious diseases including seasonal influenza. In this study, we developed noble metal (Au, Pt) nanoparticle-latex nanocomposite particles for use as probes for immunochromatographic test (ICT) strips. The nanocomposite particles were conjugated with monoclonal antibody (mAb) to detect an influenza A (H1N1) antigen. For comparison, Au nanoparticles conjugated with mAb were also prepared. The lowest detectable concentrations of the influenza A antigen were found to be 6.25 × 10-3 and 2.5 × 10-2 HAU/mL for Au nanoparticle-latex and Pt nanoparticle-latex nanocomposite particles, respectively, whereas it was 4.0 × 10-1 HAU/mL for Au nanoparticles. These results clearly demonstrated that the nanocomposite probes were more sensitive than conventional nanoparticle-based probes for ICT. To expand the versatility of the nanocomposite probes, the surfaces of the probes were functionalized with biotinylated proteins to enable modification of their surfaces with desired biotinylated antibodies through biotin-avidin binding.


Assuntos
Ouro/química , Imunoensaio/métodos , Látex/química , Nanocompostos/química , Platina/química , Virologia/métodos , Antígenos Virais/análise , Diagnóstico Precoce , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Limite de Detecção
13.
Vaccine ; 36(38): 5774-5780, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30087046

RESUMO

BACKGROUND: The objective of this study was to estimate influenza vaccine effectiveness (VE) for the 2016/17 epidemic of co-circulating influenza A(H1N1)pdm09 and A(H3N2) viruses in Beijing, the capital of China. METHODS: The surveillance-based study included all swabbed patients through influenza virological surveillance, between November 2016 and April 2017. A test-negative case-control design was used to estimate influenza VE against medically-attended laboratory-confirmed influenza in outpatient settings. Cases were influenza-like illness (ILI) patients who tested positive for influenza, and controls were influenza negative patients. RESULTS: A total of 10,496 ILI patients were enrolled and swabbed. Among them, 735 tested positive for influenza A(H1N1)pdm09, 1851 for A(H3N2), and 40 for type B. Of the 45 randomly selected specimens out of 1851 influenza A(H3N2) viruses, 2(4.4%) belonged to the H3N2 3C.2a1 clade, and 43(95.6%) belonged to A/Hong Kong/4801/2014-like 3C.2a clade. Among the 43 viruses of the 3C.2a clade, 32 viruses clustered in one subgroup carrying T131K, R142K and R261Q substitutions. The adjusted VE against all influenza was low at 25% (95% confidence interval (CI): 0-43%), with 54% (95%CI: 22-73%) for influenza A(H1N1)pdm09, and 2% (95%CI: -35% to 29%) for influenza A(H3N2). CONCLUSIONS: Our study suggested a moderate VE against influenza A(H1N1)pdm09, but low VE against influenza A(H3N2) in Beijing, 2016/17 season. Amino acid substitutions in the hemagglutinin may contribute to the low VE against influenza A(H3N2) for this season.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Potência de Vacina , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/genética , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Vigilância de Evento Sentinela , Inquéritos e Questionários , Vacinação , Adulto Jovem
14.
Arch Virol ; 163(11): 3035-3049, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30066273

RESUMO

The emergence of swine-origin pandemic H1N1 (pH1N1) in 2009 invigorated extensive surveillance programs worldwide which have resulted in the deposition of large numbers of H1N1 sequences to Genbank. In the present study, we report on global evolution and dynamics of the pandemic H1N1 influenza Hemagglutinin (HA) protein in viruses isolated from three different continents (North America, Europe and Asia) during the period between April 2009 until April 2017. Close to 2000 HA full protein sequences were downloaded from the Influenza Research Database of the NCBI and analyzed using DNAStar to run an alignment, the web-based NetNglyc to predict N-Glycosylation sites and finally, the BEAST software package to calculate evolution and substitution rates. Our analysis improves upon other published papers in that we report on frequencies, dynamics and impact of HA mutations in pH1N1 viruses isolated from three continents during the past decade, as well as the evolution rate and site-specific selection pressures. Sequence based analysis demonstrated substantial changes in the HA protein over the last decade. Results showed that the HA gene is under negative selection (P value; HA= -2.253). The evolution rates varied among the three continents ranging from 2.36 × 10-3 in Europe to 3.18 × 10-3 in Asia. Mutations were detected at higher frequency and faster rate at the antigenic sites surrounding the receptor-binding domain (RBD), in particular, in the Sa and Sb sites. Mutations were either gradually accumulated to become fixed in currently circulating strains (D114N, S179N, S202T, S220T, I233T, K300E and E391K) or dynamic in terms of appearance and disappearance, both spatially and temporally (A203T, N458K and E508G). Some of the reported mutations have been shown to increase infection severity (D239G/N; globular head), enhance HA binding affinity to its receptor (S200P and S202T; RBD), or have deleterious effect on HA function (N458K and E508G; stem region). The continuous accumulation of mutations at the Sa site led to the gradual acquisition of glycosylation at residue 179 starting from 2015, which became a dominant feature in all strains isolated in the following years. In addition to sharing common amino acid substitutions (e.g. S179N in HA head and E516K in HA stem) with previous seasonal strains, the pattern of glycosylation acquisition/loss at 177 and 179 positions on the globular head, which are prominent features of immune escape, implicate that pH1N1 might follow a similar evolution trend as the SC1918 pandemic virus.


Assuntos
Evolução Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/química , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Mutação , Infecções por Orthomyxoviridae/virologia , Filogenia , Suínos
15.
Emerg Infect Dis ; 24(8): 1536-1540, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30015611
16.
MBio ; 9(3)2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871917

RESUMO

The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region's diverse canine populations, and the zoonotic risk as the viruses continue to evolve.IMPORTANCE Mammals have emerged as critically underrecognized sources of influenza virus diversity, including pigs that were the source of the 2009 pandemic and bats and bovines that harbor highly divergent viral lineages. Here, we identify two reassortant IAVs that recently host switched from swine to canines in southern China, including one virus with known zoonotic potential. Three additional genotypes were generated via reassortment events in canine hosts, demonstrating the capacity of dogs to serve as "mixing vessels." The continued expansion of IAV diversity in canines with high human contact rates requires enhanced surveillance and ongoing evaluation of emerging pandemic threats.


Assuntos
Evolução Molecular , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/isolamento & purificação , Animais , Bovinos , Doenças dos Bovinos/virologia , China , Doenças Transmissíveis Emergentes/virologia , Doenças do Cão/virologia , Cães , Variação Genética , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Filogenia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Suínos , Doenças dos Suínos/virologia , Zoonoses/virologia
18.
Virus Res ; 250: 43-50, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29608996

RESUMO

It was previously shown that the seasonal H1N1 influenza virus antigenic drift occurred at a slower rate than the seasonal H3N2 virus during the first decade of the 21th century. It was hypothesized that the slower antigenic evolution led to a decrease in average ages of infection, which in turn resulted in lower level of global viral circulation. It is unclear what caused the difference between the two viruses, but a plausible explanation may be related to the fact that the H1N1 virus had been in human population for much longer than the H3N2 virus. This would suggest that H1N1 antigenic drift in an earlier period may have been different from a more recent period. To test this hypothesis, we analyzed seasonal H1N1 influenza sequences during various time periods. In comparison to more recent H1N1 virus, the older H1N1 virus during the first half of the 20th century showed evidences of higher nonsynnonymous/synonymous ration (dN/dS) in its hemagglutinin (HA) gene. We compared amino acid sequence changes in the HA epitopes for each outbreak season and found that there were less changes in later years. Amino acid sequence diversity in the epitopes as measured by sequence entropy became smaller for each passing decade. These suggest that there might be some limit to the antigenic drift. The longer an influenza virus has drifted in human population, the less flexibility it may become. With less flexibility to adapt and escape the host immunity, the virus may have to rely more on younger naïve population.


Assuntos
Variação Antigênica , Epitopos/genética , Evolução Molecular , Deriva Genética , Vírus da Influenza A Subtipo H1N1/genética , Antígenos Virais/genética , Surtos de Doenças , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Influenza Humana/virologia , Filogenia , Estações do Ano , Análise de Sequência de DNA , Fatores de Tempo
19.
Emerg Microbes Infect ; 7(1): 47, 2018 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-29593225

RESUMO

To elucidate the adaptive strategies of influenza A viruses (IAVs) to human, we proposed a computational approach to identify human-adaptive mutations in seasonal IAVs, which have not been analyzed comprehensively. We compared representative PB2 sequences of 1425 avian IAVs and 2176 human IAVs and identified a total of 42 human-adaptive markers, including 28 and 31 markers in PB2 proteins of seasonal viruses H1N1 and H3N2, respectively. Notably, this comprehensive list encompasses almost all the markers identified in prior computational studies and 21 novel markers including an experimentally verified mutation K526R, suggesting the predictive power of our method. The strength of our analysis derives from the enormous amount of recently available sequences as well as the recognition that human-adaptive mutations are not necessarily conserved across subtypes. We also utilized mutual information to profile the inter-residue coevolution in PB2 protein. A total of 35 and 46 coevolving site pairs are identified in H1N1 and H3N2, respectively. Interestingly, 13 out of the 28 (46.4%) identified markers in H1N1 and 16 out of the 31 (51.6%) in H3N2 are embraced in the coevolving pairs. Many of them are paired with well-characterized human-adaptive mutations, indicating potential epistatic effect of these coevolving residues in human adaptation. Additionally, we reconstructed the PB2 evolutionary history of seasonal IAVs and demonstrated the distinct adaptive pathway of PB2 segment after reassortment from H1 to H3 lineage. Our study may provide clues for further experimental validation of human-adaptive mutations and shed light on the human adaptation process of seasonal IAVs.


Assuntos
Adaptação Biológica/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Aviária/virologia , Influenza Humana/virologia , RNA Replicase/genética , Análise de Sequência , Proteínas Virais/genética , Animais , Aves/virologia , Evolução Molecular , Genoma Viral , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A/genética , Influenza Aviária/transmissão , Influenza Humana/transmissão , Mutação , Vírus Reordenados/genética , Estações do Ano
20.
J Virol ; 92(11)2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29540597

RESUMO

Influenza A(H1) viruses circulating in swine represent an emerging virus threat, as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from the classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus, A/Iowa/39/2015, as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets. The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Preexisting immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015.IMPORTANCE Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine. To understand the genetic and virologic characteristics of a virus (A/Ohio/09/2015) associated with a fatal infection and a virus associated with a nonfatal infection (A/Iowa/39/2015), we performed genome sequence analysis, antigenic testing, and pathogenicity and transmission studies in a ferret model. Reverse genetics was employed to identify a single antigenic site substitution (HA G155E) responsible for antigenic variation of A/Ohio/09/2015 compared to related classical swine influenza A(H1N1) viruses. Ferrets with preexisting immunity to the pandemic A(H1N1) virus were challenged with A/Ohio/09/2015, demonstrating decreased protection. These data illustrate the potential for currently circulating swine influenza viruses to infect and cause illness in humans with preexisting immunity to H1N1 pandemic 2009 viruses and a need for ongoing risk assessment and development of candidate vaccine viruses for improved pandemic preparedness.


Assuntos
Variação Antigênica/genética , Furões/virologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/genética , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/veterinária , Animais , Variação Antigênica/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Suínos/virologia , Doenças dos Suínos/virologia
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