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1.
Mol Biomed ; 2(1): 29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34766005

RESUMO

In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection. Supplementary Information: The online version contains supplementary material available at 10.1186/s43556-021-00054-z.

2.
Natl Sci Rev ; 8(8): nwab053, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34676098

RESUMO

Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

3.
Microbiol Spectr ; 9(2): e0059021, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34550000

RESUMO

To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P < 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. IMPORTANCE The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Criança , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Memória Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Signal Transduct Target Ther ; 6(1): 271, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267185

RESUMO

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Adolescente , Adulto , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Signal Transduct Target Ther ; 6(1): 165, 2021 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-33895786

RESUMO

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Simulação por Computador , Reposicionamento de Medicamentos , Modelos Biológicos , SARS-CoV-2/metabolismo , Humanos
6.
Nat Med ; 27(6): 1062-1070, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33888900

RESUMO

An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 µg or 30 µg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older adults (aged 65-85 years) to each treatment group (ChiCTR2000034825). BNT162b1 encodes the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) and is one of several messenger RNA-based vaccine candidates under clinical investigation. Local reactions and systemic events were generally dose dependent, transient and mild to moderate. Fever was the only grade 3 adverse event. BNT162b1 induced robust interferon-γ T cell responses to a peptide pool including the RBD in both younger and older Chinese adults, and geometric mean neutralizing titers reached 2.1-fold (for younger participants) and 1.3-fold (for the older participants) that of a panel of COVID-19 convalescent human sera obtained at least 14 d after positive SARS-CoV-2 polymerase chain reaction test. In summary, BNT162b1 has an acceptable safety profile and produces high levels of humoral and T cell responses in an Asian population.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , RNA Mensageiro/genética , RNA Mensageiro/imunologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Adulto Jovem
7.
J Virol ; 95(4)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33219167

RESUMO

Among seven coronaviruses that infect humans, three (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of human coronavirus NL63 (HCoV-NL63). Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low-pathogenicity human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo models of human airway epithelia, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry into the host cell by interaction with the S protein.IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of an HTCC compound, previously developed by us, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses-SARS-CoV-2 and MERS-CoV.


Assuntos
COVID-19/tratamento farmacológico , Quitosana/análogos & derivados , Infecções por Coronavirus/tratamento farmacológico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , COVID-19/epidemiologia , COVID-19/virologia , Quitosana/farmacologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Pandemias , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/virologia , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos
8.
Mol Biomed ; 2(1): 29, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-35006430

RESUMO

In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

9.
J Infect Dis ; 222(5): 746-754, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32563194

RESUMO

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.


Assuntos
Quimiocinas/sangue , Infecções por Coronavirus/sangue , Citocinas/sangue , Pneumonia Viral/sangue , Adulto , Betacoronavirus/isolamento & purificação , COVID-19 , Quimiocina CCL2/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/sangue , Carga Viral
10.
Emerg Infect Dis ; 25(6): 1192-1195, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31107220

RESUMO

Human infections with vaccinia virus (VACV), mostly from laboratory accidents or contact with infected animals, have occurred since smallpox was eradicated in 1980. No recent cases have been reported in China. We report on an outbreak of VACV from occupational exposure to rabbit skins inoculated with VACV.


Assuntos
Surtos de Doenças , Exposição Ocupacional , Vírus Vaccinia , Vaccinia/epidemiologia , Vaccinia/virologia , Acidentes de Trabalho , Adulto , Animais , China/epidemiologia , Genes Virais , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Coelhos , Vaccinia/história , Vaccinia/transmissão , Vírus Vaccinia/classificação , Vírus Vaccinia/genética , Adulto Jovem
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(1): 78-82, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30914117

RESUMO

Objective To select and express single-chain fragment variable (scFv) against the envelope glycoprotein Gn of severe fever with thrombocytopenia syndrome virus (SFTSV). Methods Specific anti-SFTSV-Gn antibodies were isolated from scFv library against SFTSV after four rounds of "adsorption-elution-amplification" using SFTSV-Gn protein as immobilized antigen. Monoclonal phage enzyme linked immunosorbent assay (phage-ELISA) was performed for the phage antibodies on randomly picked single colonies from the screened library. The positive scFv against SFTSV-Gn protein was transformed into the BL21 E.coli cells for its prokaryotic expression, which was identified by Western blot analysis. The binding activity of purified scFv was tested by ELISA. Results Three different scFv specific for SFTSV-Gn protein were obtained and further expressed in BL21(DE3). Western blot analysis confirmed the prokaryotic expression of the anti-SFTSV-Gn antibody. ELISA demonstrated that the anti-SFTSV-Gn scFv had binding affinity with SFTSV-Gn. Conclusion The scFv against SFTSV has been selected and expressed successfully.


Assuntos
Phlebovirus , Trombocitopenia , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática , Glicoproteínas , Humanos
12.
PLoS Negl Trop Dis ; 12(6): e0006603, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29940000

RESUMO

BACKGROUND: A cluster of eleven patients, including eight family members and three healthcare workers with fever and thrombocytopenia occurred in Yixing County, Jiangsu Province, China, from October to November 1996. However, the initial investigation failed to identify its etiology. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS bunyavirus (SFTSV), which was first discovered in 2009. The discovery of novel SFTSV resulted in our consideration to test SFTSV on the remaining samples of this cluster in September 2010. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed the epidemiological and clinical data of this cluster. The first case, one 55-year-old man with fulminant hemorrhagic diseases, died on October 14, 1996. His younger brother (the second case) developed similar hemorrhagic diseases after nursing him and then died on November 3. From November 4 to November 15, nine other patients, including six family members and three medical staffs, developed fever and thrombocytopenia after exposure to the second case. The sera of six patients were collected on November 24, 1996. IgM antibodies against SFTSV were detected in all of the six patients' sera using enzyme-linked immunosorbent assay (ELISA), while IgG antibodies were detected in one patient's serum using an indirect immunofluorescence assay (IFA). We also found that IgG antibodies against SFTSV were still detected in four surviving patients' sera 14 years after illness onset. CONCLUSIONS AND SIGNIFICANCE: The mysterious pathogen of the cluster in 1996 was proved to be SFTSV on the basis of its epidemiological data, clinical data and serological results. It suggests that SFTSV has been circulating in China for more than 10 years before being identified in 2009, and SFTSV IgG antibodies can persist for up to 14 years.


Assuntos
Infecções por Bunyaviridae/epidemiologia , Phlebovirus/imunologia , Trombocitopenia/epidemiologia , Adulto , Infecções por Bunyaviridae/virologia , China/epidemiologia , Análise por Conglomerados , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-Idade , Phlebovirus/isolamento & purificação , Estudos Retrospectivos , Trombocitopenia/virologia , Adulto Jovem
13.
Luminescence ; 33(3): 574-581, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29350441

RESUMO

A rapid and sensitive two-step time-resolved fluorescence immunoassay (TRFIA) was developed for the detection of Shiga toxin 2 (Stx2) and its variants in Shiga toxin-producing Escherichia coli (STEC) strains. In sandwich mode, a monoclonal antibody against Stx2 was coated on a microtiter plate as a capture antibody. A tracer antibody against Stx2 labeled with europium(III) (Eu3+ ) chelate was then used as a detector, followed by fluorescence measurements using time-resolved fluorescence. The sensitivity of Stx2 detection was 0.038 ng/ml (dynamic range, 0.1-1000 ng/ml). The intra- and inter-assay coefficients of variation of the assay were 3.2% and 3.6%, respectively. The performance of the established assay was evaluated using culture supernatants of STEC strains, and the results were compared to those of a common HRP (horseradish peroxidase) labeling immunosorbent assay. A polymerase chain reaction (PCR) for the detection of genes encoding Stx1 and Stx2 was used as the reference for comparison. Correlation between the Stx2-specific TRFIA and PCR was calculated by the use of kappa statics, exhibiting a perfect level of agreement. The availability of the sensitive and reliable Stx2-specific TRFIA method for quantifying Stx2 and its variants in STEC strains will complement bacteria isolation-based platform and aid in the accurate and prompt diagnosis of STEC infections.


Assuntos
Fluorimunoensaio/métodos , Toxina Shiga II/análise , Escherichia coli Shiga Toxigênica/metabolismo , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Calibragem , Ensaio de Imunoadsorção Enzimática , Európio/química , Fluorimunoensaio/instrumentação , Limite de Detecção , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Toxina Shiga I/genética , Toxina Shiga II/genética , Toxina Shiga II/imunologia , Escherichia coli Shiga Toxigênica/genética
14.
Sci Bull (Beijing) ; 63(16): 1043-1050, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32288966

RESUMO

Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets (LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry (chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.

15.
Sci Rep ; 7(1): 6503, 2017 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-28747674

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne viral disease with high mortality. Since January 2010, we have conducted an epidemiological surveillance and etiological study of SFTS in Jiangsu and Anhui provinces. From January 2010 through December 2015, a total of 286 SFTS cases were confirmed in Jiangsu and Anhui provinces with a case fatality rate of 16.1%. The majority of confirmed SFTS cases were distributed in the border area of Jiangsu and Anhui provinces. Our findings suggest that the SFTS prevalence rate rose since 2010 and reached its highest in 2015. Phylogenetic analysis demonstrated that the majority of the SFTSV strains (83.6%) from Jiangsu and Anhui provinces belonged to genotypes A and D. Notably, we identified three strains of SFTSV clustered into the genotype E. This is the first report of the genotype E SFTSV strains in mainland of China. A reassortment between genotype A and D was found in the central region of the endemic areas, where three SFTSV genotypes (A, C and D) were co-circulating.


Assuntos
Genótipo , Febre por Flebótomos/epidemiologia , Febre por Flebótomos/virologia , Phlebovirus/classificação , Phlebovirus/genética , Vírus Reordenados/classificação , Vírus Reordenados/genética , Adolescente , Adulto , Idoso , China/epidemiologia , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Phlebovirus/isolamento & purificação , Filogenia , Prevalência , Vírus Reordenados/isolamento & purificação , Análise de Sobrevida , Topografia Médica , Adulto Jovem
16.
Arch Virol ; 162(11): 3305-3312, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28707271

RESUMO

Metagenomic analysis through high-throughput sequencing is a tool for detecting both known and novel viruses. Using this technique, a novel circular single-stranded DNA (ssDNA) virus genome was discovered in respiratory secretions from a febrile traveler. The virus, named human respiratory-associated PSCV-5-like virus (HRAPLV), has a genome comprising 3,018 bases, with two major putative ORFs inversely encoding capsid (Cap) and replicase (Rep) protein and separated by two intergenic regions. One stem-loop structure was predicted in the larger intergenic region (LIR). The predicted amino acid sequences of the Cap and Rep proteins of HRAPLV showed highest identity to those of porcine stool-associated circular virus 5 isolate CP3 (PoSCV 5) (53.0% and 48.9%, respectively). The host tropism of the virus is unknown, and further study is warranted to determine whether this novel virus is associated with human disease.


Assuntos
Circovirus/genética , Circovirus/isolamento & purificação , DNA Circular/genética , DNA de Cadeia Simples/genética , DNA Viral/genética , Faringe/virologia , Genoma Viral , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia
17.
Infect Dis Poverty ; 6(1): 78, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28569189

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified emerging infectious disease, which is caused by a novel bunyavirus (termed SFTSV) in Asia. Although mosquitoes have not been identified as the primary vectors, as revealed by epidemiological surveys, their role in transmitting this SFTSV as a suspicious vector has not been validated. FINDINGS: In this study, we conducted experimental infections of mosquitoes with SFTSV to examine the role of mosquitoes in the transmission of the virus. We did not detect viral replication in Culex pipiens pallens, Aedes aegyptis and Anopheles sinensis as revealed by qRT-PCR assay. In addition, we failed to isolate SFTSV from the Vero cells cultured with suspensions of SFTSV-infected mosquitoes. CONCLUSION: The results of the present study demonstrate little possibility that mosquitoes act as vectors for the emerging pathogen SFTSV.


Assuntos
Aedes/virologia , Anopheles/virologia , Culex/virologia , Phlebovirus/fisiologia , Replicação Viral , Animais , Infecções por Arbovirus/transmissão , Arbovírus/crescimento & desenvolvimento , Arbovírus/fisiologia , Infecções por Bunyaviridae/transmissão , Chlorocebus aethiops , Phlebovirus/crescimento & desenvolvimento , Células Vero
18.
PLoS Negl Trop Dis ; 9(10): e0004092, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26485390

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent for the fatal life-threatening infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was first identified in the central and eastern regions of China. Although the viral RNA was detected in free-living and parasitic ticks, the vector for SFTSV remains unsettled. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, an experimental infection study in goats was conducted in a bio-safety level-2 (BSL-2) facility to investigate virus transmission between animals. The results showed that infected animals did not shed virus to the outside through respiratory or digestive tract route, and the control animals did not get infected. Then, a natural infection study was carried out in the SFTSV endemic region. A cohort of naïve goats was used as sentinel animals in the study site. A variety of daily samples including goat sera, ticks and mosquitoes were collected for viral RNA and antibody (from serum only) detection, and virus isolation. We detected viral RNA from free-living and parasitic ticks rather than mosquitoes, and from goats after ticks' infestation. We also observed sero-conversion in all members of the animal cohort subsequently. The S segment sequences of the two recovered viral isolates from one infected goat and its parasitic ticks showed a 100% homology at the nucleic acid level. CONCLUSIONS/SIGNIFICANCE: In our natural infection study, close contact between goats does not appear to transmit SFTSV, however, the naïve animals were infected after ticks' infestation and two viral isolates derived from an infected goat and its parasitic ticks shared 100% of sequence identity. These data demonstrate that the etiologic agent for goat cohort's natural infection comes from environmental factors. Of these, ticks, especially the predominant species Haemaphysalis longicornis, probably act as vector for this pathogen. The findings in this study may help local health authorities formulate and focus preventive measures to contain this infection.


Assuntos
Vetores Aracnídeos , Infecções por Bunyaviridae/veterinária , Doenças das Cabras/etiologia , Phlebovirus/isolamento & purificação , Carrapatos/virologia , Animais , Cabras , RNA Viral/análise
19.
Genome Announc ; 2(5)2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25291762

RESUMO

The genome sequence of the strain A/chicken/Changzhou/C08/2013 (H9N9) shows that the hemagglutinin (HA) genes of this strain are closely related to those of the strain A/chicken/Shanghai/1107/2013 (H9N2) and share 99.2% nucleotide homology, while the other seven genes had the greatest sequence identities with the novel H7N9 virus. We speculate that this strain may be a novel natural reassortant avian influenza virus (AIV).

20.
Nat Commun ; 5: 3142, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24457975

RESUMO

Influenza A (H7N9) virus has been causing human infections in China since February 2013, raising serious concerns of potential pandemics. Previous studies demonstrate that human infection is directly linked to live animal markets, and that the internal genes of the virus are derived from H9N2 viruses circulating in the Yangtze River Delta area in Eastern China. Here following analysis of 109 viruses, we show a much higher genetic heterogeneity of the H7N9 viruses than previously reported, with a total of 27 newly designated genotypes. Phylogenetic and genealogical inferences reveal that genotypes G0 and G2.6 dominantly co-circulate within poultry, with most human isolates belonging to the genotype G0. G0 viruses are also responsible for the inter- and intra-province transmissions, leading to the genesis of novel genotypes. These observations suggest the province-specific H9N2 virus gene pools increase the genetic diversity of H7N9 via dynamic reassortments and also imply that G0 has not gained overwhelming fitness and the virus continues to undergo reassortment.


Assuntos
Heterogeneidade Genética , Subtipo H7N9 do Vírus da Influenza A/genética , Vírus Reordenados/genética , Animais , Surtos de Doenças , Humanos , Subtipo H7N9 do Vírus da Influenza A/classificação , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Influenza Humana/virologia , Dados de Sequência Molecular , Filogenia
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