RESUMEN
Etiologic studies of acute febrile disease were conducted in sites across South America, including Cusco and Iquitos, Peru. Patients' clinical signs and symptoms were recorded, and acute- and convalescent-phase serum samples were obtained for serologic examination and virus isolation in Vero E6 and C6/36 cells. Virus isolated in Vero E6 cells was identified as encephalomyocarditis virus (EMCV) by electron microscopy and by subsequent molecular diagnostic testing of samples from 2 febrile patients with nausea, headache, and dyspnea. The virus was recovered from acute-phase serum samples from both case-patients and identified with cardiovirus-specific reverse transcription-PCR and sequencing. Serum samples from case-patient 1 showed cardiovirus antibody by immunoglobulin M ELISA (acute phase <8, convalescent phase >1,024) and by neutralization assay (acute phase <10, convalescent phase >1,280). Serum samples from case-patient 2 did not contain antibodies detectable by either assay. Detection of virus in serum strongly supports a role for EMCV in human infection and febrile illness.
Asunto(s)
Infecciones por Cardiovirus/etiología , Enfermedades Transmisibles Emergentes/etiología , Virus de la Encefalomiocarditis/patogenicidad , Enfermedad Aguda , Adulto , Animales , Anticuerpos Antivirales/sangre , Secuencia de Bases , Infecciones por Cardiovirus/inmunología , Infecciones por Cardiovirus/virología , Chlorocebus aethiops , Enfermedades Transmisibles Emergentes/inmunología , Enfermedades Transmisibles Emergentes/virología , Cartilla de ADN/genética , Virus de la Encefalomiocarditis/clasificación , Virus de la Encefalomiocarditis/genética , Virus de la Encefalomiocarditis/ultraestructura , Femenino , Fiebre/etiología , Fiebre/inmunología , Fiebre/virología , Humanos , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Perú , Filogenia , Vigilancia de la Población , ARN Viral/genética , ARN Viral/aislamiento & purificación , Células VeroRESUMEN
A recombinant vaccinia virus encoding rotavirus protein NSP3 driven by an internal ribosome entry site (IRES) from the encephalomyocarditis (EMC) virus was able to abate protein synthesis in BSC1 cells by 25-fold, with as much as 30% of the remaining protein synthesis being NSP3. Hence NSP3 shuts off host cell protein synthesis down to the level seen during rotavirus infection but is unable to prevent translation from EMC IRES-driven genes. This effect was abolished by deletions in the eIF4G-binding (aa 274-313) and the dimerization (aa 150-206) but not the viral mRNA-binding (aa 83-149) domains, supporting that NSP3 functions in vivo as a dimer. Binding of eIF4G by NSP3 has been implicated in interfering with mRNA 5'-3' circularization, hence such circularization is essential for translation in mammalian cells.