Antiviral activity of alpha interferon in Sindbis virus-infected cells is restored by anti-E2 monoclonal antibody treatment.
Pretreatment of AT3 rat prostatic carcinoma cells expressing the inhibitor of apoptosis bcl-2 (AT3-bcl-2 cells) with alpha interferon (IFN-alpha) affected replication of a virulent strain of Sindbis virus (SV) but did not protect against virus-induced cell death. Treatment of cells with IFN-alpha late during infection affected ongoing SV replication very little. Previous studies have shown that cross-linking of the viral glycoprotein E2 with antibody delays the inhibition of K+ influx by improving the function of Na+K+ATPase and the Na(+)-K(+)-2Cl-cotransport system in SV-infected cells (P. Després, J. W. Griffin, and D. E. Griffin, J. Virol. 69:7006-7014, 1995). In these studies, we have shown that treatment of infected cells with anti-E2 monoclonal antibody also restored the ability of IFN-alpha to induce antiviral activity in infected cells late during infection. The very low rate of virus release in SV-infected cells treated simultaneously with anti-E2 monoclonal antibody and IFN-alpha was postulated to be linked to inhibition of virus maturation. Synergistic effects of antibody and IFN-alpha are likely to be important for control of SV replication in vivo.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D011471:Prostatic Neoplasms; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins; D012845:Sindbis Virus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000276:immunology / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D007370:Interferon Type I; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C064950:glycoprotein E2, Sindbis virus