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2.
Front Immunol ; 12: 646673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367126

RESUMO

Background: Infliximab is effective in inducing and maintaining remission in patients with Crohn's disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD. Methods: From January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study. Serum samples were collected at baseline and week 2 of infliximab treatment. Serum levels of 35 cytokines were assessed in 18 patients from the discovery cohort and were further evaluated in the 60-patient cohort 1. Then, candidate cytokines and other serological biomarkers were used to construct a predictive model by logistic regression in a 182-patient cohort 2. PNR was defined based on the change of CD activity index or clinical symptoms. Results: Among the 35 cytokines, matrix metalloproteinase 3(MMP3) and C-C motif ligand 2 (CCL2) were two effective serum biomarkers associated with PNR in both the discovery cohort and cohort 1. In cohort 2, serum level of MMP3, CCL2 and C-reactive protein (CRP) at 2 weeks after infliximab injection were independent predictors of PNR, with odds ratios (95% confidence interval) of 1.108(1.059-1.159), 0.940(0.920-0.965) and 1.102(1.031-1.117), respectively. A PNR classifier combining these three indicators had a large area under the curve [0.896(95% CI:0.895-0.897)] and negative predictive value [0.918(95%CI:0.917-0.919)] to predict PNR to infliximab. Conclusions: MMP3, CCL2, and CRP are promising biomarkers in prediction of PNR to infliximab, and PNR classifier could accurately predict PNR and may be useful in clinical practice for therapy selection.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimiocina CCL2/sangue , Doença de Crohn/tratamento farmacológico , Infliximab/uso terapêutico , Metaloproteinase 3 da Matriz/sangue , Adolescente , Adulto , Estudos de Coortes , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Citocinas/sangue , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Modelos Logísticos , Masculino , Modelos Biológicos , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
3.
Sci Transl Med ; 13(606)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34285130

RESUMO

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.


Assuntos
COVID-19 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , Cricetinae , Humanos , Camundongos , Subunidades Proteicas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
4.
Theranostics ; 11(13): 6607-6615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995679

RESUMO

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo. Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.


Assuntos
COVID-19/imunologia , Modelos Animais de Doenças , Pulmão/patologia , Mucosa Respiratória/citologia , SARS-CoV-2/imunologia , Feto Abortado , Animais , COVID-19/patologia , COVID-19/virologia , Células Cultivadas , Células Epiteliais/virologia , Xenoenxertos , Humanos , Pulmão/imunologia , Pulmão/virologia , Transplante de Pulmão , Masculino , Camundongos , Camundongos SCID , Cultura Primária de Células , SARS-CoV-2/patogenicidade , Replicação Viral
5.
Signal Transduct Target Ther ; 6(1): 136, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790236

RESUMO

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.


Assuntos
COVID-19 , SARS-CoV-2/metabolismo , Caracteres Sexuais , Animais , COVID-19/metabolismo , COVID-19/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Masculino , Mesocricetus
6.
Therap Adv Gastroenterol ; 13: 1756284820979442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425010

RESUMO

Background: Recent evidence has shown that the complete blood count (CBC) is abnormal in patients with Crohn's disease (CD). We aimed to investigate an effective CBC parameter and explore its impact on disease activity in a large CD cohort. Methods: We performed a retrospective analysis of patients with established CD who underwent clinically indicated endoscopy at four tertiary centres in China between 2016 and 2020. Individual variables of the Simple Endoscopic Score for CD, CBC parameters, C-reactive protein (CRP) levels, erythrocyte sedimentation rate, and faecal calprotectin (FC) were independently reviewed by different investigators. The hold-out method was used to verify the predictive power of the established model. Results: Data from a total of 1388 endoscopic procedures performed for 882 eligible CD patients were available with routine blood parameters and related indicators. The model using platelet-to-lymphocyte percentage ratio (PLpR) had high accuracy for identifying patients in endoscopic remission (ER), with an area under the curve (AUC) of 0.785 [95% confidence interval (CI): 0.784-0.787], which was comparable with that for CRP (AUC: 0.775, 95% CI: 0.774-0.777). Notably, the AUC of PLpR was significantly higher than that of CRP in patients with colonic disease and with a history of surgery. Moreover, after combining the FC with PLpR, the AUC value of FC + PLpR increased up to 0.892 (95% CI: 0.890-0.894) for identifying ER. Conclusions: We explored an index (PLpR) to identify CD patients in ER based on platelet and lymphocyte percentage from the CBC. PLpR helped evaluate the degree of disease activity and monitor the therapeutic response.

7.
J Infect Dis ; 217(3): 438-442, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28973317

RESUMO

Pregnancy has been associated with severe influenza, an association highlighted during the 2009 pandemic of influenza A(H1N1) virus (A[H1N1]pdm09) infection. To assess the underlying mechanism, we infected pregnant and non-pregnant ferrets with A(H1N1) pdm09 virus. A(H1N1)pdm09-infected pregnant ferrets also had higher levels of inflammatory cytokines in their pulmonary tracts. Systemically, total CD8+ T cell counts and A(H1N1)pdm09-specific B-cell responses in blood were significantly lower in pregnant ferrets. This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response.


Assuntos
Citocinas/metabolismo , Vírus da Influenza A Subtipo H1N1/imunologia , Infecções por Orthomyxoviridae/patologia , Complicações Infecciosas na Gravidez/patologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Feminino , Furões , Pulmão/patologia , Pulmão/virologia , Infecções por Orthomyxoviridae/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia
8.
Invest New Drugs ; 35(5): 566-575, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28631095

RESUMO

The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro. And the effect of rAAV-DCN on the intratumoral uptake of paclitaxel was also studied in neuroblastoma-grafted nude mice. Overall, 12.5%, 17.7%, and 71.9% of the tumors stained positive for DCN, SPARC and stabilin-1 respectively and correlated to age, stage and N-MYC status in 96 children and adolescents with neuroblastoma. Transfected neuroblastoma cells stably expressed DCN, with in vivo and in vitro studies demonstrating rAAV-DCN sensitized the anticancer effect of nab-paclitaxel. Systemic rAAV-DCN in neuroblastoma-grafted nude mice inhibited stabilin-1, up-regulated SPARC, and increased the intratumoral uptake of paclitaxel. Macrophage depletion or anti-stabilin-1 monoclonal antibody increased the intratumoral uptake of nab-paclitaxel and its anticancer effects to a degree comparable to that achieved by systemic rAAV-DCN. The systemic administration of rAAV-DCN up-regulates DCN in neuroblastoma and accelerates the intratumoral uptake of nab-paclitaxel by inhibiting stabilin-1 mediated SPARC degradation.


Assuntos
Albuminas/farmacologia , Moléculas de Adesão Celular Neuronais/genética , Decorina/genética , Dependovirus/genética , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Paclitaxel/farmacologia , Receptores de Retorno de Linfócitos/genética , Regulação para Cima/genética , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mosquitos Vetores/genética , Transfecção/métodos , Regulação para Cima/efeitos dos fármacos
9.
Cancer Sci ; 108(7): 1485-1492, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28498513

RESUMO

Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be upregulated in neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1 or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel-induced autophagy and enhanced the anticancer effects of paclitaxel in normal control cancer cells but not in cells with upregulated Beclin 1 and TRP14 expression. Our findings showed that paclitaxel-induced autophagy in neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize neuroblastoma cells to paclitaxel by specifically inhibiting TRP14.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácidos Hidroxâmicos/farmacologia , Neuroblastoma , Tiorredoxinas/metabolismo , Autofagia/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Microscopia Confocal , Microscopia Eletrônica de Varredura , Neuroblastoma/metabolismo , Paclitaxel/farmacologia , Vorinostat
10.
Am J Cancer Res ; 7(2): 334-345, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28337381

RESUMO

Neuroblastoma stem cells (NSCs) can cause drug resistance and tumor recurrence. This study aimed to enhance the lytic effect of dendritic cells (DCs) co-cultured with cytokine-induced killer (CIK) cells. NSCs were obtained by suspension culture, and DC-CIK cells were loaded with extracted NSC membrane-based microparticles (MMPs) before evaluating the lytic effect of DC-CIK cells on NSCs. After inhibiting the function or expression of human leukocyte antigen-E (HLA-E) in NSCs by anti-HLA-E monoclonal antibody or siRNA, the DC-CIK cell lytic effect on NSCs was re-assessed. NSC nestin expression was high, but glial fibrillary acid protein expression and class IIIß-tubulin-1 expression were low. Moreover, NSCs exhibited strong tumorigenic ability in nude mice. Loading DCs with NSC-derived MMPs induced the differentiation of DCs and CIK cells and enhanced the killing of NSCs by DC-CIK cells. Inhibiting the function or expression of HLA-E in NSCs further enhanced the cytolytic capability of DC-CIK cells loaded with NSC-derived MMPs. HLA-E inhibitor can enhance the killing of NSC by DC-CIK cells loaded with NSC-derived MMPs.

11.
J Virol ; 90(7): 3506-14, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26764002

RESUMO

UNLABELLED: The H9N2 influenza viruses that are enzootic in terrestrial poultry in China pose a persistent pandemic threat to humans. To investigate whether the continuous circulation and adaptation of these viruses in terrestrial poultry increased their infectivity to pigs, we conducted a serological survey in pig herds with H9N2 viruses selected from the aquatic avian gene pool (Y439 lineage) and the enzootic terrestrial poultry viruses (G1 and Y280 lineages). We also compared the infectivity and transmissibility of these viruses in pigs. It was found that more than 15% of the pigs sampled from 2010 to 2012 in southern China were seropositive to either G1 or Y280 lineage viruses, but none of the sera were positive to the H9 viruses from the Y439 lineage. Viruses of the G1 and Y280 lineages were able to infect experimental pigs, with detectable nasal shedding of the viruses and seroconversion, whereas viruses of the Y439 lineage did not cause a productive infection in pigs. Thus, adaptation and prevalence in terrestrial poultry could lead to interspecies transmission of H9N2 viruses from birds to pigs. Although H9N2 viruses do not appear to be continuously transmissible among pigs, repeated introductions of H9 viruses to pigs naturally increase the risk of generating mammalian-adapted or reassorted variants that are potentially infectious to humans. This study highlights the importance of monitoring the activity of H9N2 viruses in terrestrial poultry and pigs. IMPORTANCE: H9N2 subtype of influenza viruses has repeatedly been introduced into mammalian hosts, including humans and pigs, so awareness of their activity and evolution is important for influenza pandemic preparedness. However, since H9N2 viruses usually cause mild or even asymptomatic infections in mammalian hosts, they may be overlooked in influenza surveillance. Here, we found that the H9N2 viruses established in terrestrial poultry had higher infectivity in pigs than those from aquatic birds, which suggests that adaptation of the H9N2 viruses in terrestrial poultry might have increased the infectivity of the virus to mammals. Therefore, monitoring the prevalence and evolution of H9 viruses prevalent in terrestrial birds and conducting risk assessment of their threat to mammals are critical for evaluating the pandemic potential of this virus.


Assuntos
Vírus da Influenza A Subtipo H9N2/patogenicidade , Influenza Aviária/transmissão , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/veterinária , Doenças das Aves Domésticas/transmissão , Doenças dos Suínos/virologia , Animais , Embrião de Galinha , China , Humanos , Influenza Aviária/virologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Aves Domésticas/virologia , Doenças das Aves Domésticas/virologia , Suínos
12.
Bing Du Xue Bao ; 31(4): 357-62, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26524907

RESUMO

To explore the impact of the history of infection by the influenza A virus subtype H1N1 on secondary infection by the influenza A virus subtype H9N2, pigs non-infected and pre-infected with H1N1 were inoculated with H9N2 in parallel to compare nasal shedding and seroconversion patterns. Unlike pigs without a background of H1N1 infection, nasal shedding was not detected in pigs pre-infected with H1N1. Both groups generated antibodies against H9N2. However, levels of H1N1 antibodies in pigs pre-infected with H1N1 increased quickly and dramatically after challenge with H9N2. Cross-reaction was not observed between H1N1 antibodies and H9N2 viruses. These findings suggest that circulation of the H1N1 virus might be a barrier to the introduction and transmission of the avian H9N2 virus, thereby delaying its adaptation in pigs.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H9N2/imunologia , Infecções por Orthomyxoviridae/imunologia , Suínos/imunologia , Suínos/virologia , Animais , Anticorpos Antivirais/imunologia , Reações Cruzadas , Soros Imunes/imunologia , Infecções por Orthomyxoviridae/sangue , Especificidade da Espécie
13.
J Biomed Sci ; 22: 86, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26475357

RESUMO

BACKGROUND: We have shown previously that microvesicle (MV)-delivered miR-130b (miR-130b-MV) is able to target PPAR-γ and subsequently reduce the lipid accumulation in vitro. However, the in vivo effect of miR-130b on fat deposition and glucose homeostasis remains unknown. RESULTS: Three-week-old C57BL/6 mice were fed a high-fat diet for 8 weeks and then intravenously injected with MV-packaged scrambled control microRNA (miRNA) or miR-130b every other day for 10 days. Glucose tolerance test was performed and body weight, epididymal fat weight, as well as the expression of lipid metabolic genes were determined. We showed that mice fed on high-fat diet for 8 weeks demonstrated significantly higher body weight, elevated blood glucose and impaired glucose tolerance. miR-130b-MV injection significantly reduced body weight and epididymal fat weight and partly restored glucose tolerance. miR-130b expression was significantly increased in the epididymal fat after miR-130b-MV injection while the protein content of its target gene PPAR-γ was significantly suppressed, together with a significant up-regulation of the lipolysis genes, hormone sensitive lipase, monoglyceride lipase and leptin. Moreover, miR-130b-MV injection increased the expression of miR-378a and miR-378-3p that are reported to participate in the regulation of fat deposition. CONCLUSION: Our results indicate that miR-130b-MV is able to reduce the epididymal fat deposition and partly restore glucose tolerance, through translational repression of PPAR-γ in a high-fat diet-induced obese mouse model.


Assuntos
Gorduras na Dieta/efeitos adversos , Portadores de Fármacos/farmacologia , MicroRNAs/farmacologia , Obesidade/tratamento farmacológico , PPAR gama/biossíntese , Biossíntese de Proteínas/efeitos dos fármacos , Animais , Gorduras na Dieta/farmacologia , Portadores de Fármacos/química , Lipólise/efeitos dos fármacos , Masculino , Camundongos , MicroRNAs/química , Obesidade/induzido quimicamente , Obesidade/metabolismo
14.
Sci Rep ; 5: 14170, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26391278

RESUMO

The ongoing avian H7N9 influenza outbreaks in China have caused significant human fatal cases and the virus is becoming established in poultry. Mutations with potential to increase mammalian adaptation have occurred in the polymerase basic protein 2 (PB2) and other viral genes. Here we found that dual 627K and 701N mutations could readily occur during transmission of the virus among ferrets via direct physical contact, and these mutations conferred higher polymerase activity and improved viral replication in mammalian cells, and enhanced virulence in mice. Special attention needs to be paid to patients with such mutations, as these may serve as an indicator of higher virus replication and increased pathogenicity.


Assuntos
Códon , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Mutação , Infecções por Orthomyxoviridae/virologia , RNA Polimerase Dependente de RNA/genética , Proteínas Virais/genética , Animais , Modelos Animais de Doenças , Ativação Enzimática , Furões , Humanos , Camundongos , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/transmissão , RNA Polimerase Dependente de RNA/metabolismo , Recombinação Genética , Temperatura , Tropismo Viral , Virulência/genética , Replicação Viral , Eliminação de Partículas Virais
16.
J Infect Dis ; 201(10): 1522-6, 2010 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-20370480

RESUMO

The replication activity of 2009 pandemic H1N1 influenza virus in human lung cells was evaluated in this study. Twenty-two surgically removed human lung tissue samples were infected ex vivo with pandemic H1N1 influenza virus (A/California/04/2009), seasonal human H1N1 influenza virus (A/Shantou/92/09), or a highly pathogenic H5N1 influenza virus (A/Vietnam/1194/04). Examination of nucleoprotein expression and viral RNA replication in the infected human lung tissue samples showed that whereas the replication of pandemic H1N1 influenza virus varied between tissue samples, overall this virus replicated more efficiently than seasonal H1N1 influenza virus but less efficiently than H5N1 influenza virus. Double-immunostaining for viral antigens and cellular markers indicated that pandemic H1N1 influenza virus replicates in type 2 alveolar epithelial cells.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/epidemiologia , Pulmão/virologia , Replicação Viral/fisiologia , Células Cultivadas , Surtos de Doenças , Regulação Viral da Expressão Gênica/fisiologia , Humanos , Influenza Humana/virologia , Nucleoproteínas/genética , Nucleoproteínas/metabolismo , RNA Viral/metabolismo
17.
Virology ; 401(1): 1-5, 2010 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-20303563

RESUMO

A lysine at the 627 position (627K) of PB2 protein of influenza virus has been recognized as a determinant for host adaptation and a virulent element for some influenza viruses. While seasonal influenza viruses exclusively contained 627K, the pandemic (H1N1) 2009 possessed a glutamic acid (627E), even after circulation in humans for more than 6months. To explore the potential role of E627K substitution in PB2 in the pandemic (H1N1) 2009 virus, we compared pathogenicity and growth properties between a recombinant virus containing 627K PB2 gene and the parental A/California/4/2009 strain containing 627E. Our results showed that substitution of 627K in PB2 gene does not confer higher virulence and growth rate for the pandemic (H1N1) 2009 virus in mice and cell culture respectively, suggesting 627K is not required for human adaptation of the pandemic (H1N1) 2009 virus.


Assuntos
Surtos de Doenças , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , Proteínas Virais/genética , Substituição de Aminoácidos , Animais , Linhagem Celular , Cães , Feminino , Humanos , Influenza Humana/epidemiologia , Lisina/genética , Camundongos , Camundongos Endogâmicos BALB C , Virulência/genética , Replicação Viral
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