The mechanism of inhibition of reovirus replication by interferon

Abstract

Experiments were carried out to identify the reovirus function that is the primary target for inhibition in interferon-treated cells. The two earliest functions, adsorption and conversion of parental virions to subviral particles, were completely resistant to interferon. The transcription of early messenger RNA was slightly sensitive; the transcription of all 10 species of single-stranded RNA was inhibited by 15–25% at 75 PRD 50/ml and by 50–60% at 300 PRD 50/ml interferon. No RNA species of abnormal size were detected in interferon-treated cells. Subviral particles isolated from cells treated with 300 PRD 50/ml interferon transcribed RNA as actively as subviral particles isolated from normal cells. The translation of early messenger RNA was inhibited much more severely, the degree of inhibition for the individual messenger RNA species ranging from 36 to 72% at 75 PRD 50/ml interferon. The most sensitive species was that which codes for polypeptide λ1. Three late functions, namely, the formation of progeny double-stranded RNA, the transcription of late messenger RNA, and the formation of infectious progeny, were all about as sensitive (75–90% inhibition at 75 PRD 50/ml interferon) as the translation of polypeptide λ1. This polypeptide is a constituent of double-stranded RNA-synthesizing structures, without the formation of which no late reovirus functions can be expressed. The results supported the conclusion that the reason why the replication of reovirus is inhibited in cells treated with interferon is that in such cells the translation of early reovirus mRNA, particularly that which codes for polypeptide λ1, is suppressed.