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1.
Intervirology ; 51(4): 217-23, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18781076

RESUMEN

The aim of the present study is to investigate changes of interferon (IFN) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (PBMCs) with severe acute respiratory syndrome (SARS) coronavirus (CoV) and to compare these changes to those induced by well-established IFN-inducing viruses, such as vesicular stomatitis (VSV) and Newcastle viruses (NDV). Experiments have been carried out using PBMCs of 10 different healthy donors. The results showed that the antiviral activity of IFN contained in the supernatant of SARS-CoV-infected PBMCs was lower than those induced by VSV and NDV. Consequently, SARS-CoV induces a lower synthesis of IFN-alpha, -beta and -gamma compared to VSV and NDV. Characterization of the profile of IFN-alpha subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-alpha2 and -6 subtypes were higher compared to other IFN-alpha subtypes namely, IFN-alpha5, -8, -10, -13/1, -17, and -21. In conclusion, SARS-CoV induces IFNs to a less extent compared to VSV and NDV, thus suggesting that the IFN system does play a limited role in early host defense against SARS-CoV infection.


Asunto(s)
Interferones/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Células Cultivadas , Perfilación de la Expresión Génica , Humanos , Interferones/biosíntesis , Virus de la Enfermedad de Newcastle/inmunología , Vesiculovirus/inmunología
2.
Intervirology ; 50(2): 156-60, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17191018

RESUMEN

Interferon (IFN)-alpha, -beta and -gamma have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (SARS-CoV) replication in Vero cell lines. We investigated the combination of type I IFNs (IFN-alpha or -beta) and IFN-gamma for antiviral activity and found that such combinations synergistically inhibited SARS-CoV replication in Vero cells, using yield reduction assay and the isobologram and combination index methods of Chou and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I IFNs and IFN-gamma parallels the marked increase in 2'-5'-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-alpha or -beta and IFN-gamma compared with the transcriptional levels obtained after stimulation with either IFN alone. These results demonstrate that SARS-CoV, although only moderately sensitive to the antiviral action of the individual types of IFN, is highly sensitive to a combination of type I and II IFNs, which suggests that such combinations may have potential in the treatment of SARS-CoV infections.


Asunto(s)
Antivirales/farmacología , Expresión Génica/efectos de los fármacos , Interferón Tipo I/farmacología , Interferón gamma/farmacología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Replicación Viral/efectos de los fármacos , 2',5'-Oligoadenilato Sintetasa/análisis , Animales , Chlorocebus aethiops , Sinergismo Farmacológico , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Células Vero
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