Mouse adenovirus type 1 replication in vitro is resistant to interferon

The effects of mouse interferon (IFN)-alpha/beta and recombinant IFN-gamma on mouse adenovirus type 1 (MAV-1) replication were investigated in single- cycle infectious virus yield reduction assays on mouse L929 cells. Viral yi elds at 3 days post-infection indicated that wt MAV-1 and pmE314, an early region 3 null mutant, were relatively insensitive to both IFN-alpha/beta an d IFN-gamma, whereas early region 1A (E1A) mutants pmE109 (null), d/E105 (c onserved region 1 deletion, CR1 Delta), d/E102 (CR2 Delta), and d/E106 (CR3 Delta) were sensitive. MAV-1 E1A that was inducibly expressed in mouse fib roblast 37.1 cells rescued vesicular stomatitis virus from the antiviral ef fect of IFN-alpha/beta but not from the antiviral effect of IFN-gamma. Inte rferon-inducible gene expression was reduced in 37.1 cells as compared to t he parental 3T6 cell line. Steady-state levels of IFN-inducible gene mRNAs were also reduced in 3T6 cells infected with the wild-type virus and pmE314 but not in cells infected with pmE109. These results suggest that the MAV- 1 E1A gene product is capable of interfering with the signaling pathways of both types of IFN, although modulation of IFN-alpha/beta antiviral activit y was more pronounced. (C) 2000 Academic Press.