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1.
Virus Genes ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519961

RESUMO

H9N2 subtype avian influenza virus has dramatically evolved and undergone extensive reassortment since its emergence in early 1990s in China. The genotype S (G57), emerging in 2007 with the substitution of F98-like PB2 and M gene by G1-like ones, has become the overwhelming predominant genotype for the past 11 years since 2010. Here, we found that virus with G1-like PB2 were more efficient in protein expression and in infectious virus production than that with F98-like PB2 gene. By coinfected MDCK cells with the reassortant virus, more survival opportunity for viruses with G1-like PB2 than that of F/98-like was observed. Besides, in animal experiments, we found that the G1-like PB2 increases virus infectivity, replication, and virus shedding of H9N2 in chickens. Our results suggested that the substitution of G1-like PB2 play important role in promoting the fitness of genotype S H9N2 virus in China.

2.
Virulence ; 12(1): 2443-2460, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34517783

RESUMO

A growing body of evidence suggests the pivotal role of long non-coding RNA (lncRNA) in influenza virus infection. Based on next-generation sequencing, we previously demonstrated that Lnc45 was distinctively stimulated by H5N1 influenza virus in mice. In this study, we systematically investigated the specific role of Lnc45 during influenza A virus (IAV) infection. Through qRT-PCR, we first demonstrated that Lnc45 is highly up-regulated by different subtypes of IAV strains, including H5N1, H7N9, and H1N1 viruses. Using RNA-FISH and qRT-PCR, we then found that Lnc45 can translocate from nuclear to cytoplasm during H5N1 virus infection. In addition, forced Lnc45 expression dramatically impeded viral replication of H1N1, H5N1, and H7N9 virus, while abolish of Lnc45 expression by RNA interference favored replication of these viruses, highlighting the potential broad antiviral activity of Lnc45 to IAV. Correspondingly, overexpression of Lnc45 inhibited viral polymerase activity and suppressed IAV-induced cell apoptosis. Moreover, Lnc45 significantly restrained nuclear aggregation of viral NP and PA proteins during H5N1 virus infection. Further functional study revealed that the stem ring arms of Lnc45 mainly mediated the antiviral effect. Therefore, we here demonstrated that Lnc45 functions as a broad-spectrum antiviral factor to inhibit influenza virus replication probably through inhibiting polymerase activity and NP and PA nuclear accumulation via its stem ring arms. Our study not only advances our understanding of the complexity of the IAV pathogenesis but also lays the foundation for developing novel anti-IAV therapeutics targeting the host lncRNA.

3.
Sci China Life Sci ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34542812

RESUMO

Decades have passed since the first discovery of H10-subtype avian influenza virus (AIV) in chickens in 1949, and it has been detected in many species including mammals such as minks, pigs, seals and humans. Cases of human infections with H10N8 viruses identified in China in 2013 have raised widespread attention. Two novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for AIVs. The internal genes of these viruses were derived from genotype S (G57) H9N2 and were consistent with H5N6, H7N9 and H10N8, which cause fatal infections in humans. Their viral pathogenicity and transmissibility were further studied in different animal models. The two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct contact. These viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory droplets. More importantly, these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal receptors. Asymptomatic shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.

5.
Sci Rep ; 11(1): 12636, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135395

RESUMO

Extrinsic factors, endocrine mechanisms, and behavioral indicators of migratory restlessness were studied in wintering whooper swans (Cygnus cygnus) in the Sanmenxia Swan National Wetland Park in western Henan Province, central China. First, the fecal glucocorticoid metabolite (FGM) concentration was established and related to mean air temperature or photo period (day length) using simple linear or non-linear regression models. After a model selection procedure, the best fitted model revealed that an increase of FGM concentration was associated with an increase in the squared mean air temperature (R2 = 0.88). Other models showed an increasing FGM concentration to correspond with increasing values of day length, squared day length, and mean air temperature-however without statistical support. In a second step, behavioral frequencies of seven behaviors were condensed into three behavioral principal components (PCs) using principal components analysis. Behavioral PCs largely corresponded to three activity phases described for wintering whooper swans in central China and were correlated with the FGM concentration using Spearman's rank-order correlations. Results revealed a significant correlation between FGM and behavioral PC2 (positive factor loadings from vigilance and preening, negative loading from foraging). Finally, we tested for an effect of behavioral PCs on changes in winter home range size using a set of multiple linear regression models. Results of averaged model parameter estimates showed only the behavioral PC3 (positive factor loadings from fighting and calling, negative loading from locomotion) had a marginal significant effect on home range size. Results confirmed findings of previous studies on migratory restlessness in whooper swans. However, due to the small sample size (N = 15 weeks) the effect of PC3 on home range size was weak and should be viewed with caution.

6.
Arch Virol ; 166(8): 2217-2224, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091783

RESUMO

Swine influenza is an economically important respiratory disease in swine, but it also constantly poses a threat to human health. Therefore, developing rapid, sensitive, and efficient detection methods for swine influenza virus (SIV) is important. By aligning the haemagglutinin (HA) gene sequences of SIVs circulating in China over a 10-year period, an H1 primer-probe set targeting both Eurasian avian-like H1N1 (EA H1N1) and pandemic 2009 H1N1 ((H1N1)pdm09) lineages plus a H3 primer-probe set targeting the prevalent human-like H3N2 (HL H3N2) subtype were designed. Subsequently, a TaqMan-MGB-based duplex one-step real-time RT-PCR (RT-qPCR) assay was established and evaluated. The duplex RT-qPCR has a detection limit of 5 copies/µL of HA plasmid for EA H1N1, (H1N1)pdm09, and HL H3N2 subtype SIVs, and its overall detection sensitivity of 100% and specificity of 91.67% matches that of traditional virus isolation through chicken embryo inoculation using experimentally infected mouse lung samples. The method showed high repeatability both within run and between runs, and there was no cross-reactivity against several other porcine viruses that are commonly circulating in China. Furthermore, the duplex RT-qPCR method revealed a higher prevalence of subtype H1 than subtype H3 in 166 nasal swabs from pigs collected from one slaughterhouse between October and December 2019. This assay could be very helpful in the rapid differential detection and routine surveillance of EA H1N1, (H1N1)pdm09, and HL H3N2 SIVs in China.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Infecções por Orthomyxoviridae/diagnóstico , Animais , China , Modelos Animais de Doenças , Diagnóstico Precoce , Feminino , 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 , Camundongos , Reação em Cadeia da Polimerase Multiplex , Nariz/virologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Suínos
7.
Aging (Albany NY) ; 13(8): 11969-11987, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891564

RESUMO

Circular RNAs (circRNAs) have critical regulatory roles in tumor biology. However, their contributions in hepatocellular carcinoma (HCC) still remain enigmatic. The present study aimed to investigate the molecular mechanisms underlying the involvement of hsa_circ_0110102 in the occurrence and development of HCC. The expression level of hsa_circ_0110102 was significantly downregulated in HCC cell lines and tissues, which was associated with poor prognosis. Knockdown hsa_circ_0110102 significantly promoted cell proliferation, migration, and invasion. Moreover, the interaction between hsa_circ_0110102 and miR-580-5p was predicted and verified by luciferase assay and RNA pull-down. The findings indicated that hsa_circ_0110102 functioned as a sponge for miR-580-5p. Moreover, miR-580-5p directly bound to the 3' UTR of PPARα, which decreased the production and release of C-C chemokine ligand 2 (CCL2) in HCC cells. CCL2 could activate the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway in macrophage via FoxO1 in a p38 MAPK-dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. These results concluded that hsa_circ_0110102 acted as a sponge for miR-580-5p and inhibited CCL2 secretion into tumor microenvironment by decrease the expression of PPARα in HCC cells, then inhibited the pro-inflammatory cytokine release from macrophages by regulating the COX-2/PGE2 pathway. In conclusion, hsa_circ_0110102 served as a potential prognostic predictor or therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Ativação de Macrófagos/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/imunologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Quimiocina CCL2/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Progressão da Doença , Regulação para Baixo , Feminino , Proteína Forkhead Box O1/metabolismo , Regulação Neoplásica da Expressão Gênica/imunologia , Técnicas de Silenciamento de Genes , Humanos , Fígado/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , PPAR alfa/genética , PPAR alfa/metabolismo , Prognóstico , RNA Circular/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
8.
Virol J ; 18(1): 36, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596956

RESUMO

Influenza A virus (IAV) contains a genome with eight single-stranded, negative-sense RNA segments that encode 17 proteins. During its assembly, all eight separate viral RNA (vRNA) segments are incorporated into virions in a selective manner. Evidence suggested that the highly selective genome packaging mechanism relies on RNA-RNA or protein-RNA interactions. The specific structures of each vRNA that contribute to mediating the packaging of the vRNA into virions have been described and identified as packaging signals. Abundant research indicated that sequences required for genome incorporation are not series and are varied among virus genotypes. The packaging signals play important roles in determining the virus replication, genome incorporation and genetic reassortment of influenza A virus. In this review, we discuss recent studies on influenza A virus packaging signals to provide an overview of their characteristics and functions.


Assuntos
Genoma Viral/genética , Vírus da Influenza A/genética , Vírus da Influenza A/fisiologia , Montagem de Vírus , Genoma Viral/fisiologia , Humanos , RNA Viral/genética , Replicação Viral
9.
BMC Vet Res ; 17(1): 80, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588843

RESUMO

BACKGROUND: Genotype S H9N2 viruses have become predominant in poultry in China since 2010. These viruses frequently donate their whole internal gene segments to other emerging influenza A subtypes such as the novel H7N9, H5N6, and H10N8 viruses. We recently reported that the PB2 and M genes of the genotype S H9N2 virus, which are derived from the G1-like virus, enhance the fitness of H5Nx and H7N9 avian influenza viruses in chickens and mice. However, whether the G1-like PB2 and M genes are preferentially incorporated into progeny virions during virus reassortment remains unclear; whether the G1-like PB2 and M genes from different subtypes are differentially incorporated into new virion progeny remains unknown. RESULTS: We conducted a reassortment experiment with the use of a H7N9 virus as the backbone and found that G1-like M/PB2 genes were preferentially incorporated in progeny virions over F/98-like M/PB2 genes. Importantly, the preference varied among G1-like M/PB2 genes of different subtypes. When competing with F/98-like M/PB2 genes during reassortment, both the M and PB2 genes from the H7N9 virus GD15 showed an advantage, whereas only the PB2 gene from the H9N2 virus CZ73 and the M gene from the H9N2 virus AH320 displayed the advantage. CONCLUSION: Our findings highlight the preferential and variable advantages of H9N2-derived G1-like M and PB2 genes in incorporating them into H7N9 progeny virions over SH14-derived F/98-like M/PB2 genes.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/genética , Vírus da Influenza A Subtipo H9N2/genética , Vírus Reordenados/genética , Animais , Embrião de Galinha , Coinfecção , Cães , Genótipo , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Vírus Reordenados/crescimento & desenvolvimento , Proteínas da Matriz Viral/genética , Vírion
10.
Vet Res ; 52(1): 8, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33436086

RESUMO

Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/metabolismo , Influenza Aviária/virologia , Células A549/virologia , Animais , Embrião de Galinha/virologia , Galinhas , Glicosilação , Testes de Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/fisiologia , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/fisiologia , Influenza Aviária/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia , Reação em Cadeia da Polimerase em Tempo Real
11.
Transbound Emerg Dis ; 68(2): 730-741, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32677729

RESUMO

In recent years in China, clade 2.3.4.4 H5N6 plus clade 2.3.2.1 H5N1 subtype highly pathogenic avian influenza (HPAI) viruses have gradually become endemic in poultry, and their co-circulation could inevitably facilitate the gene reassortment between each other. During our routine surveillance in live poultry markets (LPMs) in eastern China in 2017-2018, a novel reassortant H5N6 strain with the HA gene derived from clade 2.3.2.1 was isolated from the cloacal swabs of apparently healthy ducks. Phylogenetic tracing analysis indicated that another two clade 2.3.2.1 H5N1 strains with divergent lineages of PB1 gene and one clade 2.3.4.4 H5N6 isolate of the dominant genotype sharing spatio-temporal proximity were intimately involved in the generation of this rarely reported clade 2.3.2.1 H5N6 reassortant. Distinct with the other three HPAI H5 viruses showing moderate virulence in mice, the H5N1 strain of the homologous internal gene constellation against the clade 2.3.2.1 H5N6 reassortant was highly pathogenic, which might probably attribute to the H3 subtype-derived PB1 gene. However, as compared to the clade 2.3.4.4 H5N6 ancestor, the clade 2.3.2.1 H5N6 reassortant displayed a broader tissue distribution and higher viral titres in mice, which could likely facilitate the viral maintenance and spread in nature. Therefore, our results highlight that continuous epidemiological survey of H5 subtype HPAI viruses in LPMs needs to be strengthened to prevent the potential poultry or even public health threat of the novel reassortants from endemic viruses.


Assuntos
Vírus da Influenza A/genética , Influenza Aviária/virologia , Vírus Reordenados/genética , Animais , Galinhas/virologia , China/epidemiologia , Patos/virologia , Genes Virais , Genótipo , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Vírus da Influenza A/classificação , Vírus da Influenza A/patogenicidade , Vírus da Influenza A/fisiologia , Influenza Aviária/epidemiologia , Camundongos , Filogenia , Aves Domésticas/virologia , Vírus Reordenados/classificação , Vírus Reordenados/patogenicidade , Vírus Reordenados/fisiologia , Virulência
13.
Vet Microbiol ; 247: 108776, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768222

RESUMO

Pigeons were previously thought to be resistant to H5 viruses and to play a minimal role in spreading these viruses. In this study, we evaluated the pathogenicity of two clade 2.3.4.4 H5N6 viruses in pigeons and the potential viral transmissibility to specific-pathogen-free chickens in direct close contact with experimentally infected pigeons. No pigeons from the A/goose/Eastern China/Xin/2015 (GS/Xin) group exhibited clinical signs or mortality, and the virus was only detected in a few organs. However, 3 of 12 pigeons inoculated with the A/goose/Eastern China/0326/2015 (GS/0326) virus died, and 7 of 12 showed neurological symptoms and efficient viral replication in multiple organs. In both groups, viral shedding occurred in only some of the pigeons, the shedding period was relatively short, and the infection was not transmitted to the chickens. We also used chicken, duck, and BALB/c mouse models to evaluate the pathogenicity of the two H5N6 isolates. Both H5N6 isolates showed highly pathogenic to chickens but different degrees of pathogenicity in mice. Interestingly, in ducks, the intravenous pathogenicity index indicated that the GS/Xin isolate was low pathogenic, and the GS/0326 isolate was highly pathogenic, corresponding to the pathogenicity in pigeons. Our results indicated that the pathogenicity of the clade 2.3.4.4 H5N6 virus is diverse in pigeons, and pigeons contribute little to its transmission among poultry. However, pigeons may still be potential healthy reservoirs of the H5N6 highly pathogenic avian influenza virus.


Assuntos
Columbidae/virologia , Reservatórios de Doenças/veterinária , Vírus da Influenza A/patogenicidade , Influenza Aviária/transmissão , Doenças das Aves Domésticas/transmissão , Eliminação de Partículas Virais , Animais , Células Cultivadas , Galinhas/virologia , Cloaca/virologia , Reservatórios de Doenças/virologia , Patos/virologia , Feminino , Fibroblastos/virologia , Gansos/virologia , Vírus da Influenza A/crescimento & desenvolvimento , Influenza Aviária/virologia , Camundongos , Camundongos Endogâmicos BALB C , Orofaringe/virologia , Filogenia , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Virulência , Replicação Viral
14.
Int J Mol Sci ; 21(8)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32340172

RESUMO

Our previous study showed that glycyrrhizin (GLY) inhibited porcine epidemic diarrhea virus (PEDV) infection, but the mechanisms of GLY anti-PEDV action remain unclear. In this study, we focused on the anti-PEDV and anti-proinflammatory cytokine secretion mechanisms of GLY. We found that PEDV infection had no effect on toll-like receptor 4 (TLR4) protein and mRNA levels, but that TLR4 regulated PEDV infection and the mRNA levels of proinflammatory cytokines. In addition, we demonstrated that TLR4 regulated p38 phosphorylation but not extracellular regulated protein kinases1/2 (Erk1/2) and c-Jun N-terminal kinases (JNK) phosphorylation, and that GLY inhibited p38 phosphorylation but not Erk1/2 and JNK phosphorylation. Therefore, we further explored the relationship between high mobility group box-1 (HMGB1) and p38. We demonstrated that inhibition of HMGB1 using an antibody, mutation, or knockdown decreased p38 phosphorylation. Thus, HMGB1 participated in activation of p38 through TLR4. Collectively, our data indicated that GLY inhibited PEDV infection and decreased proinflammatory cytokine secretion via the HMGB1/TLR4-mitogen-activated protein kinase (MAPK) p38 pathway.


Assuntos
Ácido Glicirrízico/farmacologia , Proteína HMGB1/metabolismo , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Vírus da Diarreia Epidêmica Suína/fisiologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Células Cultivadas , Chlorocebus aethiops , Infecções por Coronavirus/veterinária , Suínos , Doenças dos Suínos/metabolismo , Doenças dos Suínos/virologia , Células Vero
15.
Transbound Emerg Dis ; 67(1): 263-275, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31484213

RESUMO

As one of the important control strategies for highly pathogenic avian influenza (HPAI) in China, vaccination has been implemented compulsively in poultry flocks since 2004. However, the emergence and dominance of the circulating antigenic variants require the update of vaccines periodically. In order to investigate the key molecular sites responsible for the antigenic drift, a total of 13 amino acid positions divergent between clade 2.3.4 H5 viruses and their descendent subclade 2.3.4.4 variants in or around the recognized antigenic epitopes A-E were initially identified through inspecting a comprehensive HA sequence alignment of the H5 subtype HPAI viruses. Subsequently, a panel of single-site or multi-site HA mutants was constructed by reverse genetics with two H5N1 viruses of S (clade 2.3.4) and QD1 (subclade 2.3.4.4) as the HA backbone to study their antigenic variations, respectively. The hemagglutination-inhibition assay revealed an evident impact of mutations at sites 88, 156, 205, 208, 239 and 289 to the HA antigenicity and highlighted that the amino acid substitutions located in the antigenic region B, especially the combined mutations at sites 205 and 208, were the major antigenic determinant which was also consistent with results from flow cytometry and antigenic mapping. Our findings provided more insights into the molecular mechanism of antigenic drift of the H5 subtype HPAI virus, which would be helpful for the selection of vaccine candidates and accordingly for the prevention and control of this devastating viral agent.


Assuntos
Variação Antigênica/genética , Antígenos Virais/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A/genética , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Substituição de Aminoácidos , Animais , Antígenos Virais/imunologia , China , Epitopos/imunologia , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/imunologia , Virus da Influenza A Subtipo H5N1/patogenicidade , Vírus da Influenza A Subtipo H5N8/genética , Vírus da Influenza A Subtipo H5N8/imunologia , Vírus da Influenza A Subtipo H5N8/patogenicidade , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Influenza Aviária/imunologia , Mutação , Aves Domésticas , Doenças das Aves Domésticas/imunologia , Genética Reversa
16.
Transbound Emerg Dis ; 67(2): 758-768, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31631569

RESUMO

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1-like M and PB2 genes for the earlier F/98-like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1-like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared with the F/98-like counterpart, while the G1-like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1-like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses.


Assuntos
Galinhas/virologia , Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/virologia , RNA Polimerase Dependente de RNA/genética , Vírus Reordenados , Proteínas da Matriz Viral/genética , Proteínas Virais/genética , Animais , Embrião de Galinha , Cães , Feminino , Genótipo , Células HEK293 , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/patogenicidade , Vírus da Influenza A Subtipo H9N2/fisiologia , Vírus da Influenza A/patogenicidade , Vírus da Influenza A/fisiologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Virulência
17.
Emerg Microbes Infect ; 8(1): 823-826, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31164049

RESUMO

The spread of highly pathogenic avian influenza (HPAI) H5N1 virus is associated with wild fowl migration in East Asian-Australasian (EA) and Central Asian (CA) flyways. However, the spread of H5N1 virus between the two flyways is still unclear. Here, the movements of wild waterfowl were obtained from satellite tracking data covering seven bar-headed geese and three great black-headed gulls breeding in the Qinghai Lake area (along the EA flyway), and 20 whooper swans wintering in the Sanmenxia Reservoir area (at the CA flyway). From the 2688 samples that were screened from wild birds at Qinghai Lake after an outbreak of H5N1 in July 2015, four genomes of H5N1 virus were obtained from bar-headed geese. The results of phylogenetic analysis indicated that these H5N1 viruses belonged to clade 2.3.2.1c and their gene fragments were highly homologous with A/whooper swan/Henan/SMX1/2015 (H5N1) virus (ranging from 99.76% to 100.00%) isolated from a dead whooper swan from the Sanmenxia Reservoir area along the EA flyway in January 2015. Furthermore, the coincidental timing of the H5N1 outbreak with spring migration, together with phylogenetic evidence, provided new evidence of the east-to-west spread of HPAI H5N1 between the EA and CA migratory flyways of China.


Assuntos
Anseriformes/fisiologia , Virus da Influenza A Subtipo H5N1/fisiologia , Influenza Aviária/epidemiologia , Migração Animal , Animais , Animais Selvagens/fisiologia , Animais Selvagens/virologia , Anseriformes/virologia , Ásia/epidemiologia , Austrália/epidemiologia , China/epidemiologia , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Influenza Aviária/transmissão , Influenza Aviária/virologia , Filogenia , Estações do Ano
18.
Medicine (Baltimore) ; 98(5): e13941, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702555

RESUMO

Gut flora plays an essential role in disease and health. A traditional Chinese herb formula, Dahuang Danpi Decoction (DDD) can alleviate several gastrointestinal diseases.In the present study, we assessed the effect of DDD on the growth and metabolism of Lactobacillus bulgaricus. L bulgaricus was cultured in MRS with 40 mg/ml (high), 10 mg/ml (medium), and 2.5 mg/ml (low) of DDD, Ceftriaxone and blank (control). The growth of L bulgaricus was measured by optical density. The levels of L-lactic acid and D-lactic acid were also measured.Compared to the control group, the concentrations of L bulgaricus in the medium and the high concentrations DDD groups were significantly higher (P < .001 for all), while the concentrations of L bulgaricus in the ceftriaxone groups were significantly lower. In the 3 DDD groups, the L- lactic acid levels were significantly higher than those in the control group and the ceftriaxone groups (P < .001 for all), and the L-lactic acid level was the highest in the high DDD group. Similarly, the D-lactic acid level in the high concentration DDD group was significantly higher than those in the medium and low concentration DDD groups, the control group and the ceftriaxone groups. Both the L-lactic acid and D-lactic acid levels were lower than those in the control group and the DDD groups.DDD could dose-dependently promote the growth of L bulgaricus and enhance the secretion of L-lactic acid and D-lactic acid, which suggests DDD may be able to interact with the probiotics, improve the gut microbiota, and serve in the prevention and treatment of dysbiosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus/efeitos dos fármacos , Antibacterianos/farmacologia , Ceftriaxona/farmacologia , Relação Dose-Resposta a Droga , Humanos , Ácido Láctico/biossíntese , Lactobacillus/crescimento & desenvolvimento
19.
Micromachines (Basel) ; 9(2)2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30393366

RESUMO

Pulse wave monitoring is critical for the evaluation of human health. In this paper, a wearable multi-sensor pulse wave monitoring system is proposed and demonstrated. The monitoring system consists of a measuring unit and an analog circuit processing unit. The main part of the measuring unit is a flexible printed circuit board (PCB) with a thickness of 0.15 mm, which includes three micro-electromechanical system (MEMS) pressure sensors softly packaged by polydimethylsiloxane (PDMS), a blood oxygen detector and a MEMS three-axis accelerometer. The MEMS pressure sensors,the blood oxygen detector and the accelerometer are fixed on the expected locations of the flexible PCB. The analog circuit processing unit includes a power supply module, a filter and an amplifier. The pulse waves of two volunteers are detected by the monitoring system in this study. The output signals of the analog circuit processing module are processed and analyzed. In the preliminary test, the time delay of the three pressure pulse waves has been detected and the calculated pulse wave velocities (PWVs) are 12.50 and 11.36 m/s, respectively. The K value, related to the area of the pulse wave, can be obtained. Both the PWV and K value meet the health parameter standards.

20.
Vet Microbiol ; 224: 8-16, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30269795

RESUMO

Two reassortant H5N2 viruses in which hemagglutinin (HA) was clustered into clade 2.3.4.4, were isolated from apparently healthy waterfowl in live poultry markets in Eastern China in 2016. We used specific pathogen-free chickens, mallard ducks, and BALB/c mice to evaluate the isolates' biological characteristics in different animal models. The newly isolated reassortant H5N2 viruses were able to cause severe disease in chickens and effective contact transmission, only at high doses. Our pathogenicity studies in ducks yielded an interesting result: the intravenous pathogenicity index (IVPI) indicated that isolate A/goose/Eastern China/1106/2016(1106) was low pathogenic and the other isolate A/duck/Eastern China/YD1516/2016(YD1516) was of highly pathogenicity in ducks. However, our 50% duck lethal dose (DLD50) experiment demonstrated that these viruses were all of low pathogenicity (DLD50 > 107.0 EID50) in ducks. Additionally, despite the fact that reassortant H5N2 were of low pathogenicity in mice, they could bind to both avian-type (SAα-2,3 Gal) and human-type (SAα-2,6 Gal) receptors, suggesting that these isolates still present a high risk for human infection. Therefore, it is of great importance to implement continual surveillance of avian influenza virus (AIV) to protect both veterinary and public health.


Assuntos
Galinhas/virologia , Patos/virologia , Vírus da Influenza A Subtipo H5N2/genética , Vírus da Influenza A Subtipo H5N2/patogenicidade , Influenza Aviária/virologia , Vírus Reordenados/genética , Animais , China/epidemiologia , Feminino , Genoma Viral , Hemaglutininas/genética , Humanos , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Influenza Aviária/epidemiologia , Influenza Aviária/transmissão , Camundongos , Camundongos Endogâmicos BALB C , Filogenia , Aves Domésticas/virologia , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Ligação Viral
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