Marburg Virus Viral Protein 35 Inhibits Protein Kinase R Activation in a Cell Type-Specific Manner.

Abstract

Protein kinase R (PKR) is a key antiviral protein involved in sensing and restricting viral infections. Here we analyzed the ability of Marburg virus (MARV) viral protein 35 (VP35) to inhibit PKR activation in human and bat cells. Similar to the related Ebola and Lloviu viruses, MARV VP35 was able to inhibit PKR activation in 293T cells. In contrast, we found that MARV VP35 did not inhibit human or bat PKR activation in human glioblastoma U-251-MG cells or a Rousettus aegyptiacus cell line. Additional experiments revealed that PACT, a known PKR regulator, was insufficient to rescue the ability of VP35 to inhibit PKR activation in these cells. Taken together, this study indicates that the ability of VP35 to inhibit PKR is cell type specific, potentially explaining discrepancies between the ability of filoviruses to potently block innate immune responses, and the high levels of interferon and interferon-stimulated genes observed in filovirus patients.