Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1

Abstract

We describe experiments which demonstrate that shortly after infection of Friend erythroleukemia cells with herpes simplex virus (HSV), polyribosomes dissociate and cellular mRNA degrades. Analysis of infected cell extracts on sucrose density gradients demonstrates that the majority of the polyribosomes have dissociated to monoribosomes at 2 h postinfection. Physical measurements of infected-cell RNAs support this conclusion and demonstrate that the polyadenylated RNAs decrease in size. The degradation of mRNA is apparently a stochastic process as judged by the failure to detect a shift in the Crtl/2 when

Regulation of Protein Synthesis in Virus-Infected Animal Cells

“…(2) Fenwick and Walker (1978); Stenberg and Pizer (1982). (3) Stage 1-see text; stage 2- Inglis (1982); Nishioka and Silverstein (1978b). (4) Silverstein and Engelhardt (1979).…”

“…(5) Fenwick and Walker (1978); Hackstadt and Mallavia (1982). (7) Fenwick and Walker (1978); Nishioka and Silverstein (1978b); Read and Frenkel (1983). Frog virus 3: (6) cited in Mosenkis et al (1985).…”

“…The unusual sensitivity of herpes virus mRNAs to hypertonic stress is consistent with the hypothesis that they have extensive secondary structure. The irreversible (Read and Frenkel, 1983) early shutoff of host translation by a structural component of the herpes virion also seems to involve cleavage of host mRNAs-enough to inactivate them for translation (Fenwick and McMenamin, 19841, although they can still be detected by hybridization, more or less (Nishioka and Silverstein, 1978b;Schek and Bachenheimer, 1985). Since mutants that are defective in stageone shutoff can still induce secondary shutoff of host protein synthesis (Read and Frenkel, 19831, two distinct viral gene products, either nucleases or activators thereof, are apparently involved.…”

Herpes simplex virus types 1 and 2 induce shutoff of host protein synthesis by different mechanisms in Friend erythroleukemia cells

“…The effects of viral infection on cellular macromolecular synthesis induced by Herpes simplex viruses type 1 (HSV-1) or HSV-2 have been extensively documented (10,18,(22)(23)(24)34). Shortly after infection with either HSV-1 or HSV-2, cellular polysomes disaggregate (10,19,34,35), and host protein synthesis begins an irreversible decline (10,18,23,34). In addition, HSV-1 causes the dissociation of cellular mRNA from the polysomes (19), degrades host RNA (17,19,32), inhibits the synthesis of cellular DNA (24) and RNA (32), and reduces glycosylation of cellular proteins (30).…”

“…More recent investigations have raised doubts concerning this simple picture of HSV-induced shutoff. Nishioka and Silverstein reported two distinct shutoff functions in HSV-1 (19). One, a virion-associated component, causes extensive disaggregation of host polyribosomes, but surprisingly little loss of globin synthesis in induced Friend erythroleukemia cells (FL cells).…”