I haven’t had time to blog in a long time. But I have been doing a lot of writing. Writing can sometimes be very soothing. Other times it gives you a buzz. But right now it is driving me absolutely crazy. Here is a sample:
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent (MVvac) virus, and C-deficient virus grows poorly relative to the parental virus. Here we show that a major effector of the C-phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNAi-mediated knockdown (“PKRkd cells”), we show that a reduction in PKR partially rescues the growth defect of Cko virus, but has no effect on growth of either WT or Vko viruses. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased PKR and eIF-2a phosphorylation. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells compared to PKR-sufficient cells. Although apoptosis induced by infection of PKR-sufficient cells with the Cko virus was blocked by the caspase antagonist z-VAD-fmk, growth of Cko virus was not rescued by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection, but that the virus growth restriction by PKR is not dependent upon induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the pro-apoptotic and antiviral activities of PKR.
If you made it this far in this post, you’re probably thinking two things:
(1) What on earth is z-VAD-fmk?
(2) This girl has got to be crazy.