VSVΔG MARV GP and VSVΔG ZEBOV GP induce strong and rapid anti-viral state in mouse peritoneal macrophages through type I interferon stimulation (128.11)

• Published in: The Journal of immunology (1950) Vol. 182; no. 1_Supplement; pp. 128 - 128.11
• Main Authors: Silaghi, Alex, Fernando, Lisa, Alimonti, Judie, Stroeher, Ute, Feldmann, Heinz, Jones, Steven M
• Format: Journal Article
• Language: English
• Published: 01.04.2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.128.11

Abstract Replacement of Vesicular Stomatitis Virus (VSV) G protein with the Marburg (MARV) and Ebola (ZEBOV) viruses' glycoproteins (GP) led to the most effective experimental post-exposure therapeutics available against filoviruses. We hypothesize that the therapeutic effect is partly dependent on activation of innate immune mechanisms, as animals die before the adaptive immune response is activated. Macrophages are primary target cells of MARV, ZEBOV and the recombinant VSVs. Thus, we investigated the innate anti-viral mechanisms that are activated in J774A.1 murine macrophages by VSVΔG MARV GP and VSVΔG ZEBOV GP. The infections result in rapid induction of anti-viral state, as measured by resistance to challenge with a high MOI of a VSV expressing GFP. There is a significant induction of anti-viral state by 6 hours post-infection and by 24 hours post-infection the cells are almost completely resistant to subsequent infections, which correlates with phosphorylation of IRF-3 and IFN-α and IFN-β production. Blockage of the IFN-α/β Receptor, neutralizes 70%-90% of the anti-viral effects suggesting that the anti-viral state induced after VSVΔG MARV GP or VSVΔG ZEBOV GP infections are type I interferon-dependent. In conclusion, the post-exposure protection may be dependent on type I interferon induction and subsequent activation of anti-viral pathways, which may inhibit filovirus replication in target cells.