RESUMO
Ferret coronaviruses (FRCoVs) exist as an enteric and a systemic pathotype, of which the latter is highly lethal to ferrets. To our knowledge, this study provides the first full genome sequence of a FRCoV, tentatively called FRCoV-NL-2010, which was detected in 2010 in ferrets in The Netherlands. Phylogenetic analysis showed that FRCoV-NL-2010 is most closely related to mink CoV, forming a separate clade of mustelid alphacoronavirus that split off early from other alphacoronaviruses. Based on sequence homology of the complete genome, we propose that these mustelid coronaviruses may be assigned to a new species. Comparison of FRCoV-NL-2010 with the partially sequenced ferret systemic coronavirus MSU-1 and ferret enteric coronavirus MSU-2 revealed that recombination in the spike, 3c and envelope genes occurred between different FRCoVs.
Assuntos
Infecções por Coronavirus/veterinária , Coronavirus/classificação , Coronavirus/isolamento & purificação , Furões/virologia , Genoma Viral , RNA Viral/genética , Recombinação Genética , Animais , Análise por Conglomerados , Coronavirus/genética , Infecções por Coronavirus/virologia , Países Baixos , Filogenia , Análise de Sequência de DNA , Homologia de SequênciaRESUMO
The ability of Middle East respiratory syndrome coronavirus (MERS-CoV) to infect small animal species may be restricted given the fact that mice, ferrets, and hamsters were shown to resist MERS-CoV infection. We inoculated rabbits with MERS-CoV. Although virus was detected in the lungs, neither significant histopathological changes nor clinical symptoms were observed. Infectious virus, however, was excreted from the upper respiratory tract, indicating a potential route of MERS-CoV transmission in some animal species.
Assuntos
Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/crescimento & desenvolvimento , Animais , Doenças Assintomáticas , Cricetinae , Modelos Animais de Doenças , Feminino , Pulmão/patologia , Pulmão/virologia , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Coelhos , Sistema Respiratório/virologia , Eliminação de Partículas ViraisRESUMO
Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection.
Assuntos
Adenosina Desaminase/metabolismo , Infecções por Coronaviridae/enzimologia , Coronaviridae/fisiologia , Dipeptidil Peptidase 4/metabolismo , Receptores Virais/metabolismo , Internalização do Vírus , Adenosina Desaminase/genética , Sequência de Aminoácidos , Animais , Coronaviridae/genética , Infecções por Coronaviridae/virologia , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/genética , Modelos Animais de Doenças , Furões , Humanos , Dados de Sequência Molecular , Ligação Proteica , Receptores Virais/química , Receptores Virais/genética , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic stability and growth characteristics of MVA-MERS-S make it a suitable candidate vaccine for clinical testing. Vaccinated mice produced high levels of serum antibodies neutralizing MERS-CoV. Thus, MVA-MERS-S may serve for further development of an emergency vaccine against MERS-CoV.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Coronavirus/imunologia , Portadores de Fármacos/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Animais , Coronavirus/genética , Vetores Genéticos/administração & dosagem , Instabilidade Genômica , Camundongos , Camundongos Endogâmicos BALB C , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vaccinia virus/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/genéticaRESUMO
The performance of a test can be suboptimal, but in appropriate setting such a test is still useful for clinical decision making. We investigated the role of Antigen Rapid Diagnostic Test (Ag-RDT) for clinical decision making in an Emergency Department (ED) in Curacao during peak of COVID-19 pandemic. Ag-RDT was performed in the naso- and oropharynx-swabs from patients with respiratory insufficiency presented to the ED. Ag-RDT was performed in 153 patients, of which 64 (41.8%) showed positive results. Comparing Ag-RDT results with molecular tests, its sensitivity was 68.8% (95% CI 57.4 to 78.7), and specificity of 94.6% (95% CI 84.9 to 98.9). The positive and negative predictive value were 95.1% (95% CI 86.5 to 98.3) and 66.3 (95% CI 58.6 to 73.3), respectively. All patients with Ag-RDT positive test were admitted to the cohorted COVD-19 department of the hospital. By using Ag-RDT, 35.9% of rapid PCR tests (that are more costly and laborious to perform) could be avoided at cost of 5.8% patients with false positive result. In conclusion, in real practice, disease prevalence is as important as test's performance for clinical decision making. The conclusion may also be applicable for other diagnostic tests than COVID-19 diagnostic.
Assuntos
Teste para COVID-19 , COVID-19 , Tomada de Decisão Clínica , Prevalência , COVID-19/diagnóstico , Teste para COVID-19/estatística & dados numéricos , Curaçao/epidemiologia , Humanos , Pandemias , Sensibilidade e EspecificidadeAssuntos
Furões/virologia , Vírus da Hepatite E/classificação , Vírus da Hepatite E/genética , Hepatite E/veterinária , Animais , Fezes/virologia , Hepatite E/virologia , Vírus da Hepatite E/isolamento & purificação , Humanos , Dados de Sequência Molecular , Países Baixos/epidemiologia , Filogenia , Análise de Sequência de DNARESUMO
ABSTRACT The performance of a test can be suboptimal, but in appropriate setting such a test is still useful for clinical decision making. We investigated the role of Antigen Rapid Diagnostic Test (Ag-RDT) for clinical decision making in an Emergency Department (ED) in Curacao during peak of COVID-19 pandemic. Ag-RDT was performed in the naso- and oropharynxswabs from patients with respiratory insufficiency presented to the ED. Ag-RDT was performed in 153 patients, of which 64 (41.8%) showed positive results. Comparing Ag-RDT results with molecular tests, its sensitivity was 68.8% (95% CI 57.4 to 78.7), and specificity of 94.6% (95% CI 84.9 to 98.9). The positive and negative predictive value were 95.1% (95% CI 86.5 to 98.3) and 66.3 (95% CI 58.6 to 73.3), respectively. All patients with Ag-RDT positive test were admitted to the cohorted COVD-19 department of the hospital. By using Ag-RDT, 35.9% of rapid PCR tests (that are more costly and laborious to perform) could be avoided at cost of 5.8% patients with false positive result. In conclusion, in real practice, disease prevalence is as important as test's performance for clinical decision making. The conclusion may also be applicable for other diagnostic tests than COVID-19 diagnostic.
Assuntos
Infecções por Coronavirus/veterinária , Enterite/veterinária , Animais , Anticorpos Antivirais/sangue , Coronavirus/classificação , Coronavirus/genética , Coronavirus/imunologia , Coronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Enterite/diagnóstico , Enterite/epidemiologia , Enterite/terapia , Fezes/virologia , Furões/virologia , Países Baixos/epidemiologia , Filogenia , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Análise de Sequência de DNARESUMO
West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 10(5) TCID(50) Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.