Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
J Virol ; 94(1)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31597771

RESUMO

Efficient human-to-human transmission is a prerequisite for a novel influenza virus to cause an influenza pandemic; however, the genetic determinants of influenza virus transmission are still not fully understood. In this study, we compared the respiratory droplet transmissibilities of four H7N9 viruses that are genetic closely related and found that these viruses have dissimilar transmissibilities in guinea pigs: A/Anhui/1/2013 (AH/1) transmitted efficiently, whereas the other three viruses did not transmit. The three nontransmissible viruses have one to eight amino acid differences compared with the AH/1 virus. To investigate which of these amino acids is important for transmission, we used reverse genetics to generate a series of reassortants and mutants in the AH/1 background and tested their transmissibility in guinea pigs. We found that the neuraminidase (NA) of the nontransmissible virus A/chicken/Shanghai/S1053/2013 had low enzymatic activity that impaired the transmission of AH/1 virus, and three amino acid mutations-V292I and K627E in PB2 and D156E in M1-independently abolished the transmission of the AH/1 virus. We further found that an NA reassortant and three single-amino-acid mutants replicated less efficiently than the AH/1 virus in A549 cells and that the amino acid at position 156 of M1 affected the morphology of H7N9 viruses. Our study identifies key amino acids in PB2 and M1 that play important roles in H7N9 influenza virus transmission and provides new insights into the transmissibility of influenza virus.IMPORTANCE Efficient transmission is a prerequisite for a novel influenza virus to cause an influenza pandemic; however, the genetic determinants of influenza virus transmission remain poorly understood. H7N9 influenza viruses, which emerged in 2013 in China, have caused over 1,560 human infection cases, showing clear pandemic potential. Previous studies have shown that the H7N9 viruses differ in their transmissibility in animal models. In this study, we found two amino acids in PB2 (292V and 627K) and one in M1 (156D) that are extremely important for H7N9 virus transmission. Of note, PB2 292V and M1 156D appear in most H7N9 viruses, and the PB2 627K mutation could easily occur when the H7N9 virus replicates in humans. Our study thus identifies new amino acids that are important for influenza virus transmission and suggests that just a few key amino acid changes can render the H7N9 virus transmissible in mammals.

3.
Nat Microbiol ; 4(8): 1268-1273, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31036910

RESUMO

Here, we developed hCK, a Madin-Darby canine kidney (MDCK) cell line that expresses high levels of human influenza virus receptors and low levels of avian virus receptors. hCK cells supported human A/H3N2 influenza virus isolation and growth much more effectively than conventional MDCK or human virus receptor-overexpressing (AX4) cells. A/H3N2 viruses propagated in hCK cells also maintained higher genetic stability than those propagated in MDCK and AX4 cells.


Assuntos
Células Madin Darby de Rim Canino/virologia , Orthomyxoviridae/genética , Orthomyxoviridae/isolamento & purificação , Animais , Antígenos CD/metabolismo , Linhagem Celular , Cães , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana , Mutação , Receptores Virais/genética , Receptores Virais/metabolismo , Sialiltransferases/genética , Sialiltransferases/metabolismo
4.
Sci China Life Sci ; 62(1): 76-83, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30515728

RESUMO

Antigenic drift forces us to frequently update influenza vaccines; however, the genetic basis for antigenic variation remains largely unknown. In this study, we used clade 7.2 H5 viruses as models to explore the molecular determinants of influenza virus antigenic variation. We generated eight monoclonal antibodies (MAbs) targeted to the hemagglutinin (HA) protein of the index virus A/chicken/Shanxi/2/2006 and found that two representative antigenically drifted clade 7.2 viruses did not react with six of the eight MAbs. The E131N mutation and insertion of leucine at position 134 in the HA protein of the antigenically drifted strains eliminated the reactivity of the virus with the MAbs. We also found that the amino acid N131 in the H5 HA protein is glycosylated. Our results provide experimental evidence that glycosylation and an amino acid insertion or deletion in HA influence antigenic variation.


Assuntos
Aminoácidos/imunologia , Antígenos Virais/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Sequência de Aminoácidos , Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Antígenos Virais/genética , Antígenos Virais/metabolismo , Galinhas/virologia , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/metabolismo , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/metabolismo , Influenza Aviária/genética , Influenza Aviária/imunologia , Influenza Aviária/virologia , Influenza Humana/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Homologia de Sequência de Aminoácidos
5.
Adv Mater ; 30(8)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29315853

RESUMO

Two series of new polymers with medium and wide bandgaps to match fullerene (PC71 BM) and fullerene-free 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITIC) acceptors are designed and synthesized, respectively. For constructing the key donor building blocks, the effective symmetry-breaking strategy is employed. Two common aromatic rings (thiophene and benzene) are chosen as one side substituted groups in the asymmetric benzodithiophene (BDT) monomers. In addition, another rigid benzene ring is inserted between aryl and thioether in the side chains, which results in larger twisting and destroying the aggregation and forming longer lever arms. As a result, highly ordered polymers (PBDTsTh-FBT and PBDTsPh-FBT) with strong aggregation properties can blend well with roughly spherical PC71 BM, while amorphous polymers (PBDTsThPh-BDD and PBDTsPhPh-BDD) with long and rigid aryl rings show good miscibility with elongated ITIC, and finally, both devices exhibit excellent power conversion efficiencies over 10%. Thus, it clearly shows that the asymmetric BDT unit is an excellent donor building block to construct highly efficient photovoltaic polymers. Meanwhile, this work demonstrates that it is not necessary that high-performance fullerene-free polymer solar cells (PSCs) require highly ordered microstructures in the blending films, different from the fullerene-based PSCs.

6.
Cell Res ; 27(12): 1409-1421, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29151586

RESUMO

Certain low pathogenic avian influenza viruses can mutate to highly pathogenic viruses when they circulate in domestic poultry, at which point they can cause devastating poultry diseases and severe economic damage. The H7N9 influenza viruses that emerged in 2013 in China had caused severe human infections and deaths. However, these viruses were nonlethal in poultry. It is unknown whether the H7N9 viruses can acquire additional mutations during their circulation in nature and become lethal to poultry and more dangerous for humans. Here, we evaluated the evolution of H7N9 viruses isolated from avian species between 2013 and 2017 in China and found 23 different genotypes, 7 of which were detected only in ducks and were genetically distinct from the other 16 genotypes that evolved from the 2013 H7N9 viruses. Importantly, some H7N9 viruses obtained an insertion of four amino acids in their hemagglutinin (HA) cleavage site and were lethal in chickens. The index strain was not lethal in mice or ferrets, but readily obtained the 627K or 701N mutation in its PB2 segment upon replication in ferrets, causing it to become highly lethal in mice and ferrets and to be transmitted efficiently in ferrets by respiratory droplet. H7N9 viruses bearing the HA insertion and PB2 627K mutation have been detected in humans in China. Our study indicates that the new H7N9 mutants are lethal to chickens and pose an increased threat to human health, and thus highlights the need to control and eradicate the H7N9 viruses to prevent a possible pandemic.


Assuntos
Galinhas/virologia , Subtipo H7N9 do Vírus da Influenza A/genética , Mutação , Virulência/genética , Animais , China , Humanos
7.
Adv Mater ; 28(38): 8490-8498, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27500667

RESUMO

Two 1D-2D asymmetric benzodithiophenes (BDTs) as donor building blocks are designed and synthesized, combining the advantages of both 1D and 2D symmetric BDTs. The photovoltaic properties of the asymmetric BDT-based polymers are improved greatly in comparison with corresponding symmetric BDT-based polymers. This work provides a new approach to design prospective organic optoelectronic materials employing the symmetry-breaking strategy.

8.
J Virol ; 90(21): 9797-9805, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27558424

RESUMO

The H5N1 avian influenza viruses emerged in Southeast Asia in the late 20th century and have evolved into multiple phylogenetic clades based on their hemagglutinin (HA)-encoding genes. The clade 7.2 viruses were first detected in chickens in northern China in 2006, and vaccines specifically targeted to the clade were developed and have been used in poultry in China since 2006. During routine surveillance and disease diagnosis, we isolated seven H5 viruses between 2011 and 2014 that bear the clade 7.2 HA genes. Here, we performed extensive studies to understand how the clade 7.2 H5 viruses have evolved in chickens in China. Full genome sequence analysis revealed that the seven viruses formed two subtypes (four H5N1 viruses and three H5N2 viruses) and four genotypes by deriving genes from other influenza viruses. All of the viruses had antigenically drifted from the clade 7.2 viruses that were isolated in 2006. Pathogenicity studies of four viruses, one from each genotype, revealed that all of the viruses are highly pathogenic in chickens, but none of them could replicate in ducks. The four viruses exclusively bound to avian-type receptors and replicated only in the turbinates and/or lungs of mice; none of them were lethal to mice at a dosage of 106 50% egg infective doses (EID50). Our study indicates that although the clade 7.2 viruses have not been eradicated from poultry through vaccination, they have not become more dangerous to other animals (e.g., ducks and mice) and humans. IMPORTANCE: Animal influenza viruses can acquire the ability to infect and kill humans. The H5N1 viruses have been a concern in recent decades because of their clear pandemic potential. We sorted H5N1 influenza viruses into different phylogenetic clades based on their HA genes. The clade 7.2 viruses were detected in chickens in several provinces of northern China in 2006. Vaccines for these viruses were subsequently developed and have been used ever since to control infection of poultry. Here, we analyzed the genetic and biologic properties of seven clade 7.2 viruses that were isolated from chickens between 2011 and 2014. We found that after nearly 9 years of circulation in chickens, the clade 7.2 viruses still exclusively bind to avian-type receptors and are of low pathogenicity to mice, suggesting that these H5 viruses pose a low risk to human public health.


Assuntos
Virus da Influenza A Subtipo H5N1/genética , Vírus da Influenza A Subtipo H5N2/genética , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Animais , Galinhas , China/epidemiologia , Patos/virologia , Genoma Viral/genética , Genótipo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Virus da Influenza A Subtipo H5N1/imunologia , Vírus da Influenza A Subtipo H5N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/imunologia , Filogenia , Aves Domésticas , Vacinação/métodos
9.
Proc Natl Acad Sci U S A ; 113(2): 392-7, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26711995

RESUMO

Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we performed extensive influenza surveillance in pigs in China and isolated 228 influenza viruses from 36,417 pigs. We found that 139 of the 228 strains from pigs in 10 provinces in China belong to the EAH1N1 lineage. These viruses formed five genotypes, with two distinct antigenic groups, represented by A/swine/Guangxi/18/2011 and A/swine/Guangdong/104/2013, both of which are antigenically and genetically distinct from the current human H1N1 viruses. Importantly, the EAH1N1 SIVs preferentially bound to human-type receptors, and 9 of the 10 tested viruses transmitted in ferrets by respiratory droplet. We found that 3.6% of children (≤10 y old), 0% of adults, and 13.4% of elderly adults (≥60 y old) had neutralization antibodies (titers ≥40 in children and ≥80 in adults) against the EAH1N1 A/swine/Guangxi/18/2011 virus, but none of them had such neutralization antibodies against the EAH1N1 A/swine/Guangdong/104/2013 virus. Our study shows the potential of EAH1N1 SIVs to transmit efficiently in humans and suggests that immediate action is needed to prevent the efficient transmission of EAH1N1 SIVs to humans.


Assuntos
Furões/genética , Furões/virologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/virologia , Adulto , Animais , Antígenos Virais/imunologia , China/epidemiologia , Evolução Molecular , Genótipo , Hemaglutininas/genética , Humanos , Imunidade , Vigilância Imunológica , Vírus da Influenza A Subtipo H1N1/patogenicidade , Pulmão/patologia , Pulmão/virologia , Camundongos , Pessoa de Meia-Idade , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/transmissão , Prevalência , Suínos , Virulência , Replicação Viral
10.
J Virol ; 90(3): 1455-69, 2016 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-26581996

RESUMO

UNLABELLED: H4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicating that these viruses are undergoing complex and frequent reassortment events. All 32 viruses tested could replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that the H4 AIVs bound to α-2,6-linked glycans, although they retained the binding preference for α-2,3-linked glycans. When we tested the direct-contact transmission of 10 H4 viruses in guinea pigs, we found that three viruses did not transmit to any of the contact animals, one virus transmitted to one of three contact animals, and six viruses transmitted to all three contact animals. When we further tested the respiratory droplet transmissibility of four of the viruses that transmitted efficiently via direct contact, we found that three of them could transmit to one or two of the five exposed animals. Our study demonstrates that the current circulating H4 AIVs can infect, replicate in, and transmit to mammalian hosts, thereby posing a potential threat to human health. These findings emphasize the continual need for enhanced surveillance of H4 AIVs. IMPORTANCE: Numerous surveillance studies have documented the wide distribution of H4 AIVs throughout the world, yet the biological properties of H4 viruses have not been well studied. In this study, we found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China and that H4 viruses can replicate in mice, possess human-type receptor binding specificity, and transmit between guinea pigs via direct contact. Strikingly, some H4 strains also can transmit via respiratory droplet, albeit with limited efficiency. These results clearly show the potential threat posed by H4 viruses to public health.


Assuntos
Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Infecções por Orthomyxoviridae/veterinária , Aves Domésticas/virologia , Ligação Viral , Replicação Viral , Animais , China , Análise por Conglomerados , Feminino , Genoma Viral , Cobaias , Vírus da Influenza A/genética , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Infecções por Orthomyxoviridae/transmissão , Filogenia , RNA Viral/genética , Receptores Virais/análise , Análise de Sequência de DNA , Homologia de Sequência
11.
Sci Rep ; 5: 11233, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-26058711

RESUMO

The continued spread of the newly emerged H7N9 viruses among poultry in China, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. An MF59-adjuvant H7N9 inactivated vaccine is reported to be well-tolerated and immunogenic in humans; however a study in ferrets indicated that while a single dose of the inactivated H7N9 vaccine reduced disease severity, it did not prevent virus replication and transmission. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H7N9 vaccine (H7N9/AAca) that contains wild-type HA and NA genes from AH/1, and the backbone of the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AAca). H7N9/AAca was attenuated in mice and ferrets, and induced robust neutralizing antibody responses in rhesus mice, ferrets, and guinea pigs immunized once or twice intranasally. The animals immunized twice were completely protected from H7N9 virus challenge. Importantly, the animals vaccinated once were fully protected from transmission when exposed to or in contact with the H7N9 virus-inoculated animals. These results demonstrate that a cold-adapted H7N9 vaccine can prevent H7N9 virus transmission; they provide a compelling argument for further testing of this vaccine in human trials.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/fisiologia , Vacinas Atenuadas/imunologia , Replicação Viral/imunologia , Animais , Subtipo H7N9 do Vírus da Influenza A/imunologia
12.
PLoS Pathog ; 10(11): e1004508, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25411973

RESUMO

H9N2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. Because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. Here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of H9N2 influenza viruses that were detected in live poultry markets in southern China between 2009 and 2013. Thirty-five viruses represented 17 genotypes on the basis of genomic diversity, and one specific "internal-gene-combination" predominated among the H9N2 viruses. This gene combination was also present in the H7N9 and H10N8 viruses that have infected humans in China. All of the 35 viruses preferentially bound to the human-like receptor, although two also retained the ability to bind to the avian-like receptor. Six of nine viruses tested were transmissible in ferrets by respiratory droplet; two were highly transmissible. Some H9N2 viruses readily acquired the 627K or 701N mutation in their PB2 gene upon infection of ferrets, further enhancing their virulence and transmission in mammals. Our study indicates that the widespread dissemination of H9N2 viruses poses a threat to human health not only because of the potential of these viruses to cause an influenza pandemic, but also because they can function as "vehicles" to deliver different subtypes of influenza viruses from avian species to humans.


Assuntos
Variação Genética , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Animais , Sequência de Bases , Galinhas , China , Cães , Furões , Humanos , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Vírus da Influenza A Subtipo H9N2/patogenicidade , Influenza Aviária/genética , Influenza Aviária/transmissão , Influenza Humana/genética , Influenza Humana/transmissão , Células Madin Darby de Rim Canino , Dados de Sequência Molecular , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/transmissão , Doenças das Aves Domésticas/virologia
13.
Science ; 341(6144): 410-4, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23868922

RESUMO

A newly emerged H7N9 virus has caused 132 human infections with 37 deaths in China since 18 February 2013. Control measures in H7N9 virus-positive live poultry markets have reduced the number of infections; however, the character of the virus, including its pandemic potential, remains largely unknown. We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice. Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplet. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.


Assuntos
Furões/virologia , Vírus da Influenza A/patogenicidade , Influenza Humana/transmissão , Influenza Humana/virologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Sistema Respiratório/virologia , Animais , Galinhas/virologia , Columbidae/virologia , Patos/virologia , Genes Virais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/fisiologia , Influenza Aviária/virologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Mutação , Receptores de Superfície Celular/metabolismo , Receptores Virais/metabolismo , Replicação Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA