The synergistic interaction of interferon types I and II leads to marked reduction in severe acute respiratory syndrome-associated coronavirus replication and increase in the expression of mRNAs for interferon-induced proteins.
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.
Scagnolari
Carolina
C
Department of Experimental Medicine, Virology Section, University La Sapienza, Rome, Italy.
Trombetti
Simona
S
Alberelli
Alessia
A
Cicetti
Simona
S
Bellarosa
Daniela
D
Longo
Roberta
R
Spanò
Alberto
A
Riva
Elisabetta
E
Clementi
Massimo
M
Antonelli
Guido
G
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D007370:Interferon Type I; D011506:Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase