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1.
Proc Natl Acad Sci U S A ; 117(29): 17204-17210, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32601207

RESUMO

Pigs are considered as important hosts or "mixing vessels" for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.


Assuntos
Genes Virais , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Animais , China , Reações Cruzadas , Células Epiteliais/virologia , Variação Genética , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Influenza Humana/imunologia , Influenza Humana/transmissão , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/transmissão , Pandemias , Filogenia , Prevalência , Vírus Reordenados/genética , Estudos Soroepidemiológicos , Suínos
2.
Mem Inst Oswaldo Cruz ; 115: e200009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428082

RESUMO

BACKGROUND Influenza viral load (VL) can be a decisive factor in determining the antiviral efficacy in viral clearance. OBJECTIVE This study aimed to evaluate the rate of infection and the role of influenza VL on the clinical spectrum of illnesses among different patient groups attended at a tertiary hospital in Brazil. METHODS Samples were collected from patients presenting acute respiratory infection from 2009 to 2013. Overall, 2262 samples were analysed and distributed into three groups: (i) asymptomatic (AS); (ii) symptomatic outpatients (OP); and (iii) hospitalised patients (HP). VL (expressed in Log10 RNA copies/mL) was calculated through a quantitative real-time one-step reverse transcription-polymerase chain reaction (RT-PCR) assay aimed at the M gene, with human RNAseP target as internal control and normalising gene of threshold cycle values. FINDINGS A total of 162 (7.16%) H1N1pdm09 positive samples were analysed. Patients aged from 0.08 to 77 years old [median ± standard deviation (SD): 12.5 ± 20.54]. Children with 5 to 11 years old presented the highest detection (p < 0.0001). AS patients had the lowest VL, with a significant difference when compared with symptomatic patients (p = 0.0003). A higher VL was observed within two days of disease onset. Ten patients (HP group) received antiviral treatment and were followed up and presented a mean initial VL of 6.64 ± 1.82. A complete viral clearance for 50% of these patients was reached after 12 days of treatment. MAIN CONCLUSIONS It is important to evaluate AS patients as potential spreaders, as viral shedding was still present, even at lower VL. Our results suggest that patients with underlying diseases and severe clinical symptoms may be considered for prolonged viral treatment.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Infecções Respiratórias/virologia , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Adulto Jovem
3.
PLoS One ; 15(3): e0229601, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130243

RESUMO

A community outbreak of human influenza A(H1N1)pdm09 virus strains was observed in Myanmar in 2017. We investigated the circulation patterns, antigenicity, and drug resistance of 2017 influenza A(H1N1)pdm09 viruses from Myanmar and characterized the full genome of influenza virus strains in Myanmar from in-patients and out-patients to assess the pathogenicity of the viruses. Nasopharyngeal swabs were collected from out-patients and in-patients with acute respiratory tract infections in Yangon and Pyinmana City in Myanmar during January-December 2017. A total of 215 out-patients and 18 in-patients infected with A(H1N1)pdm09 were detected by virus isolation and real-time RT-PCR. Among the positive patients, 90.6% were less than 14 years old. Hemagglutination inhibition (HI) antibody titers against A(H1N1)pdm09 viruses in Myanmar were similar to the recommended Japanese influenza vaccine strain for 2017-2018 seasons (A/Singapore/GP1908/2015) and WHO recommended 2017 southern hemisphere vaccine component (A/Michigan/45/2015). Phylogenetic analysis of the hemagglutinin sequence showed that the Myanmar strains belonged to the genetic subclade 6B.1, possessing mutations of S162N and S164T at potential antigenic sites. However, the amino acid mutation at position 222, which may enhance the severity of disease and mortality, was not found. One case with no prior history of oseltamivir treatment possessed H275Y mutated virus in neuraminidase (NA), which confers resistance to oseltamivir and peramivir with elevated IC50 values. The full genome sequence of Myanmar strains showed no difference between samples from in-patients and out-patients, suggesting no additional viral mutations associated with patient severity. Several amino acid changes were observed in PB2, PB1, and M2 of Myanmar strains when compared to the vaccine strain and other Asian strains. However, no mutations associated with pathogenicity were found in the Myanmar strains, suggesting that viral factors cannot explain the underlying reasons of the massive outbreak in Myanmar. This study reported the first detection of an oseltamivir-resistant influenza virus in Myanmar, highlighting the importance of continuous antiviral monitoring and genetic characterization of the influenza virus in Myanmar.


Assuntos
Epidemias , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Adolescente , Adulto , Substituição de Aminoácidos , Antígenos Virais , Antivirais/farmacologia , Criança , Pré-Escolar , Farmacorresistência Viral/genética , Feminino , Genoma Viral , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Mianmar/epidemiologia , Oseltamivir/farmacologia , Filogenia , Adulto Jovem
4.
Sci Rep ; 10(1): 4510, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161289

RESUMO

Novel H1N2 influenza A viruses (IAVs) in swine have been identified in Chile co-circulating with pandemic H1N1 2009-like (A(H1N1)pdm09-like) viruses. The objective of this study was to characterize antigenically the swine H1 IAVs circulating in Chile. Genetic analysis based on the HA1 domain and antigenic analysis by hemagglutination inhibition assay were carried out. Three antigenic clusters were identified, named Chilean H1 A (ChH1A), Chilean H1 B (ChH1B), and A(H1N1)pdm09-like. The antigenic sites of ChH1A and ChH1B strains were 10-60% distant from those of commercial vaccine strains at the amino acid sequence level. Antigenic variants were identified within the clusters ChH1A and A(H1N1)pdm09-like. Substitutions in the main antigenic sites (E153G in Sa, Q193H in Sb, D168N in Ca1, P137S in Ca2, and F71L in Cb) were detected in variants from the ChH1A cluster, whereas only a single substitution in antigenic site Sa (G155E) was detected in variants from A(H1N1)pdm09-like cluster, which confirms the importance to carrying out antigenic analyses in addition to genetic analyses to evaluate control measures such as vaccination. These results highlight the need to update vaccines for swine in Chile and the importance of continued surveillance to determine the onward transmission of antigenic variants in Chilean pig populations.


Assuntos
Antígenos Virais/imunologia , Interações Hospedeiro-Patógeno/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Sequência de Aminoácidos , Animais , Variação Antigênica , Antígenos Virais/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Filogenia , Análise de Sequência de DNA , Suínos
5.
PLoS One ; 15(2): e0228029, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045419

RESUMO

Influenza A (H1N1) pdm09 virus emerged in North America in 2009 and has been established as a seasonal strain in humans. After an antigenic stasis of about six years, new antigenically distinct variants of the virus emerged globally in 2016 necessitating a change in the vaccine formulation for the first time in 2017. Herein, we analyzed thirty-eight HA sequences of influenza A (H1N1) pdm09 strains isolated in Kenya during 2015-2018 seasons, to evaluate their antigenic and molecular properties based on the HA1 sub-unit. Our analyses revealed that the A (H1N1) pdm09 strains that circulated in Kenya during this period belonged to genetic clade 6B, subclade 6B.1 and 6B.2. The Kenyan 2015 and 2016 isolates differed from the vaccine strain A/California/07/2009 at nine and fourteen antigenic sites in the HA1 respectively. Further, those isolated in 2017 and 2018 correspondingly varied from A/Michigan/45/2015 vaccine strain at three and fifteen antigenic sites. The predicted vaccine efficacy of A/California/07/2009 against Kenyan 2015/2016 was estimated to be 32.4% while A/Michigan/45/2015 showed estimated vaccine efficacies of 39.6% - 41.8% and 32.4% - 42.1% against Kenyan 2017 and 2018 strains, respectively. Hemagglutination-inhibition (HAI) assay using ferret post-infection reference antiserum showed that the titers for the Kenyan 2015/2016 isolates were 2-8-fold lower compared to the vaccine strain. Overall, our results suggest the A (H1N1) pdm09 viruses that circulated in Kenya during 2015/2016 influenza seasons were antigenic variants of the recommended vaccine strains, denoting sub-optimal vaccine efficacy. Additionally, data generated point to a swiftly evolving influenza A (H1N1) pdm09 virus in recent post pandemic era, underscoring the need for sustained surveillance coupled with molecular and antigenic analyses, to inform appropriate and timely influenza vaccine update.


Assuntos
Antígenos Virais/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/imunologia , Filogenia , Subunidades Proteicas/imunologia , Sequência de Aminoácidos , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vacinas contra Influenza/imunologia , Quênia , Homologia de Sequência de Aminoácidos , Organização Mundial da Saúde
6.
mSphere ; 5(1)2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024713

RESUMO

While working overnight at a swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, Nanopore sequenced 13 IAV genomes from samples we collected, and predicted in real time that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current prepandemic candidate vaccine viruses (CVVs). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 h after unpacking the mobile lab. Exhibition swine are a known source for zoonotic transmission of IAV to humans and pose a potential pandemic risk. Genomic analyses of IAV in swine are critical to understanding this risk, the types of viruses circulating in swine, and whether current vaccines developed for use in humans would be predicted to provide immune protection. Nanopore sequencing technology has enabled genome sequencing in the field at the source of viral outbreaks or at the bedside or pen-side of infected humans and animals. The acquired data, however, have not yet demonstrated real-time, actionable public health responses. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes, A(H1N1), A(H3N2), and A(H1N2). Analysis of the hemagglutinin (HA) sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 of these viruses and the most closely related CVV. As an exercise in pandemic preparedness, all sequences were emailed to CDC collaborators who initiated the development of a synthetically derived CVV.IMPORTANCE Swine are influenza virus reservoirs that have caused outbreaks and pandemics. Genomic characterization of these viruses enables pandemic risk assessment and vaccine comparisons, though this typically occurs after a novel swine virus jumps into humans. The greatest risk occurs where large groups of swine and humans comingle. At a large swine exhibition, we used Nanopore sequencing and on-site analytics to interpret 13 swine influenza virus genomes and identified an influenza virus cluster that was genetically highly varied to currently available vaccines. As part of the National Strategy for Pandemic Preparedness exercises, the sequences were emailed to colleagues at the CDC who initiated the development of a synthetically derived vaccine designed to match the viruses at the exhibition. Subsequently, this virus caused 14 infections in humans and was the dominant U.S. variant virus in 2018.


Assuntos
Genoma Viral , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H3N2/genética , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , Monitoramento Epidemiológico , Variação Genética , Genótipo , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N2/classificação , Vírus da Influenza A Subtipo H3N2/classificação , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Filogenia , RNA Viral , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/transmissão , Estados Unidos/epidemiologia
7.
J Virol ; 94(8)2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-31996432

RESUMO

Genetic reassortments occurred continuously among multiple subtypes or genotypes of influenza viruses prevalent in pigs. Of note, some reassortant viruses bearing the internal genes of the 2009 pandemic H1N1 (2009/H1N1) virus sporadically caused human infection, which highlights their potential threats to human public health. In this study, we performed phylogenetic analysis on swine influenza viruses (SIVs) circulating in Liaoning Province, China. A total of 22 viruses, including 18 H1N1 and 4 H1N2 viruses, were isolated from 5,750 nasal swabs collected from pigs in slaughterhouses from 2014 to 2016. H1N1 viruses formed four genotypes, which included Eurasian avian-like H1N1 (EA H1N1) and double/triple reassortant H1N1 derived from EA H1N1, 2009/H1N1, and triple reassortant H1N2 (TR H1N2) viruses. H1N1 SIVs with different genotypes and even those within the same genotypes represented different pathogenicities in mice. We further characterized two naturally isolated H1N1 SIVs that had similar viral genomes but differed substantially in their virulence in mice and found that a single amino acid at position 431 in the basic polymerase 2 (PB2) protein significantly affected the viral replication capacity and virulence of these two viruses. Taken together, our findings revealed the diverse genomic origins and virulence of the SIVs prevalent in Liaoning Province during 2014 to 2016, which highlights that continuous surveillance is essential to monitor the evolution of SIVs. We identified a naturally occurring amino acid mutation in the PB2 protein of H1N1 SIVs that impacts the viral replication and virulence in mice by altering the viral polymerase activity.IMPORTANCE The frequent reassortment among different influenza viruses in pigs adds complexity to the epidemiology of swine influenza. The diverse viral virulence phenotypes underline the need to investigate the possible genetic determinants for evaluating the pandemic potential to human public health. Here, we found that multiple genotypes of influenza viruses cocirculate in the swine population in Liaoning Province, China. Furthermore, we pinpointed a single amino acid at position 431 in the PB2 protein which plays a critical role in the virulence of H1N1 viruses in mice and found that the alteration of viral polymerase activities is the cause of the different virulence. Our study further indicated that the virulence of influenza virus is a polygenic trait, and the newly identified virulence-related residue in the PB2 provides important information for broadening knowledge on the genetic basis of viral virulence of influenza viruses.


Assuntos
Aminoácidos/genética , Genótipo , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Filogenia , Vírus Reordenados/genética , Doenças dos Suínos/virologia , Animais , China , Modelos Animais de Doenças , Feminino , Genes Virais/genética , Genoma Viral , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H1N2/genética , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Análise de Sequência de Proteína , Suínos , Virulência/genética , Replicação Viral , Sequenciamento Completo do Genoma
8.
Emerg Infect Dis ; 25(12): 2303-2306, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742520

RESUMO

We report influenza A(H1N1)pdm09 virus infection in a captive giant panda in Hong Kong. The viral load peaked on day 1 and became undetectable on day 5, and an antibody response developed. Genome analysis showed 99.3%-99.9% nucleotide identity between the virus and influenza A(H1N1)pdm09 virus circulating in Hong Kong.


Assuntos
Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Ursidae/virologia , Animais , Linhagem Celular , Genoma Viral , Genômica , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hong Kong/epidemiologia , Masculino , Filogenia , Carga Viral
9.
Emerg Microbes Infect ; 8(1): 1456-1464, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603050

RESUMO

Pigs play an important role in interspecies transmission of the influenza virus, particularly as "mixing vessels" for reassortment. Two influenza A/H1N1 virus strains, A/swine/Siberia/1sw/2016 and A/swine/Siberia/4sw/2017, were isolated during a surveillance of pigs from private farms in Russia from 2016 to 2017. There was a 10% identity difference between the HA and NA nucleotide sequences of isolated strains and the most phylogenetically related sequences (human influenza viruses of 1980s). Simultaneously, genome segments encoding internal proteins were found to be phylogenetically related to the A/H1N1pdm09 influenza virus. In addition, two amino acids (129-130) were deleted in the HA of A/swine/Siberia/4sw/2017 compared to that of A/swine/Siberia/1sw/2016 HA.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/genética , Doenças dos Suínos/epidemiologia , Suínos/microbiologia , Animais , Genoma Viral , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Infecções por Orthomyxoviridae/epidemiologia , Filogenia , Vírus Reordenados/isolamento & purificação , Federação Russa/epidemiologia , Doenças dos Suínos/virologia
10.
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
11.
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
12.
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
13.
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
14.
Virology ; 534: 96-107, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31226666

RESUMO

Nasal wash samples from 15 human volunteers challenged with GMP manufactured influenza A/California/04/2009(H1N1) and from 5 naturally infected influenza patients of the 2009 pandemic were deep sequenced using viral targeted hybridization enrichment. Ten single nucleotide polymorphism (SNP) positions were found in the challenge virus. Some of the nonsynonymous changes in the inoculant virus were maintained in some challenge participants, but not in others, indicating that virus is evolving away from the Vero cell adapted inoculant, for example SNPs in the neuraminidase. Many SNP sites in challenge patients and naturally infected patients were found, many not identified previously. The SNPs identified, and phylogenetic analyses, showed that intrahost evolution of the virus are different in challenge participants and naturally infected patients. This study, using hybridization enrichment without PCR, provided an accurate and unbiased assessment of differential intrahost viral evolution from a uniform influenza inoculant in humans and comparison to naturally infected patients.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/virologia , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Masculino , Pessoa de Meia-Idade , Filogenia , Polimorfismo de Nucleotídeo Único , Proteínas Virais/genética , Adulto Jovem
15.
Philos Trans R Soc Lond B Biol Sci ; 374(1775): 20180257, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31056053

RESUMO

In 1918, a strain of influenza A virus caused a human pandemic resulting in the deaths of 50 million people. A century later, with the advent of sequencing technology and corresponding phylogenetic methods, we know much more about the origins, evolution and epidemiology of influenza epidemics. Here we review the history of avian influenza viruses through the lens of their genetic makeup: from their relationship to human pandemic viruses, starting with the 1918 H1N1 strain, through to the highly pathogenic epidemics in birds and zoonoses up to 2018. We describe the genesis of novel influenza A virus strains by reassortment and evolution in wild and domestic bird populations, as well as the role of wild bird migration in their long-range spread. The emergence of highly pathogenic avian influenza viruses, and the zoonotic incursions of avian H5 and H7 viruses into humans over the last couple of decades are also described. The threat of a new avian influenza virus causing a human pandemic is still present today, although control in domestic avian populations can minimize the risk to human health. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.


Assuntos
Influenza Aviária/história , Influenza Humana/história , Zoonoses/história , Animais , Aves , História do Século XX , Humanos , 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 H1N1/fisiologia , Influenza Aviária/virologia , Influenza Humana/virologia , Filogenia , Zoonoses/virologia
16.
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
17.
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
18.
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
19.
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
20.
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
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