Differential sensitivity of two related viruses, Newcastle disease virus and Sendai virus, to interferon in mouse Had-2 cells: selective inhibition of translation of NDV mRNA

Abstract

Had-2, a mouse mutant cell line derived from FM3A, constitutively releases interferon-alpha and beta and acquires resistance to Newcastle disease virus (NDV) and other viruses. However, Had-2 was found as susceptible to Sendai virus (HVJ) as FM3A. Even when Had-2 cells were infected simultaneously with NDV and HVJ, only the replication of NDV was inhibited, while that of HVJ was not. Northern blot hybridization analysis indicated that accumulation of NDV-specific primary transcripts was somewhat reduced in Had-2, but the reduction was insufficient to critically suppress the viral replication. Moreover, this decrease was not observed in the presence of cycloheximide, and a closely comparable amount of the primary transcripts was detected in both Had-2 and FM3A cells. The mRNA accumulated in the presence of cycloheximide was translated efficiently on removal of the inhibitor in FM3A cells, but not at all in Had-2 cells. Thus the translation of NDV mRNA was the major target of interferon in Had-2 cells. The fact that the synthesis of HVJ proteins was unaffected in Had-2 cells may imply that a host-cell component that distinguishes between NDV and HVJ mRNAs is involved in their translation.

Sendai Virus C Protein Plays a Role in Restricting PKR Activation by Limiting the Generation of Intracellular Double-Stranded RNA

“…This finding indicates that SeV has the ability to directly inhibit functions of antiviral proteins or to keep them inactive, consistent with a previous finding that Had-2 cells, a mouse FM3A cell line constitutively expressing IFN-␣, are susceptible to SeV but resistant to Newcastle disease virus (NDV) (1). Since this ability does not appear to be explained by the previously found IFN antagonistic abilities, we decided to investigate the mechanisms underlying this novel antagonism.…”