PKR-mediated IRF-3 phosphorylation occurs within the RIG-like
receptor-IPS adapter signal transduction pathway. A, whole cell
extracts were prepared from parental PKR+ cells, either uninfected
(–) or ΔE3L virus-infected (+) for 10 h following transient
knockdown as described under “Experimental Procedures,” utilizing
chemically synthesized siRNAs against luciferase as a control (lanes
1 and 2), IPS-1 (lanes 3 and 4), or TRIF
(lanes 5 and 6). Western immunoblot analyses were carried
out with antibodies against IRF-3, phospho-IRF-3(Ser-396), TRIF, IPS-1, and
β-actin as a loading control. B, whole cell extracts were
prepared from parental PKR+ cells infected with ΔE3L mutant
virus following transient knockdown utilizing siRNAs against the following
targets: lane 1, luciferase control; lane 2, RIG-I; lane
3, mda-5; lane 4, IPS-1; lane 5, IRF-3; lane
6, PKR; lane 7, RIG-I and mda-5. Western immunoblot analyses
were carried out with extracts prepared at 10 h after infection with
antibodies against IRF-3, IPS-1, phospho-PKR (P-PKR), PKR,
phospho-eIF-2α (P-eIF-2α), and eIF-2α or 24 h after
infection to measure PARP cleavage (PARP 85), vaccinia virus protein
expression, and β-actin.