Suppression of the Synthesis of Cellular Macromolecules by Herpes Simplex Virus

Abstract

SUMMARYSynthesis of cellular protein was substantially inhibited within I h of infection with herpes simplex virus, type 2, strain G (HSV-2). The inhibition also occurred, although no virus-specific protein synthesis was detected, after infection with u.v. irradiated virus and in cytoplasts that had been enucleated before infection. The inhibitory activity could not be distinguished from infectivity by dilution, sedimentation or reaction with y-globulin. HSV-2 also suppressed the synthesis of Sendal virus proteins, but not those specified by HSV-I.Host protein synthesis was no more sensitive than virus protein synthesis to an increased concentration of NaCI in the medium, nor could the suppression of host synthesis be prevented by adding excess MgC12 to the medium or by omitting CaC12 or NaCI. It was accompanied by the breakdown of polyribosomes, which also occurred in the presence of cycloheximide but not at 4 °C. The breakdown yielded ribosomes that were sensitive to a high salt concentration, unlike those produced by treatment of polyribosomes with RNase. The synthesis of cellular DNA and RNA was also inhibited following infection with u.v.-inactivated virus.It is concluded that the suppression of host protein synthesis (and probably also of host DNA and RNA synthesis) is caused by a constituent of the infecting virus particles. The mechanism is obscure but probably does not depend on the leakage out of the cell of Mg ~+ or into the cell of Ca 2+ or Na + ions, nor on the specific inhibition of initiation of host polypeptide chains, nor on RNase-like attack on host polyribosomes.

On the Control of Immediate Early ( ) mRNA Survival in Cells Infected with Herpes Simplex Virus

“…its own) protein synthesis, possibly destroying viral mRNA, but with diminishing effect as the mRNA-stabilizing factor is produced. After simultaneous infection with F and G the strong vhs activity of G did not reduce the synthesis of F proteins, suggesting that the inhibition applied specifically to host protein synthesis, although G was able to shut off the synthesis of both viral and cellular proteins in cells infected 7 h previously with the paramyxovirus Sendal virus (Fenwick & Walker, 1978). Similarly, in cells infected in the presence of CX with the shutoff-defective HSV-1 mutant vhs-1, and later washed and superinfected with wild-type virus in the presence of actinomycin, both cellular and mutant viral protein syntheses were suppressed (Read & Frenkel, 1983).…”

“…If virion-mediated shutoff is non-specific, the failure of G to suppress the synthesis of other viral proteins after simultaneous mixed infection (Fenwick & Walker, 1978) suggests that the early shutoff activity is transient. This is illustrated in Fig.…”

“…Many strains of HSV suppress the protein synthesis of their host cells early in infection by a mechanism apparently mediated by a component of the virus particles (Nishioka & Silverstein, 1978;Fenwick & Walker, 1978) and accompanied by degradation of mRNA (Fenwick & McMenamin, 1984;Mayman & Nishioka, 1985;Schek & Bachenheimer, 1985). Studies with a mutant of HSV-1 (KOS), vhs-1, which fails to shut off host protein synthesis, have shown that all of its mRNAs are appreciably more stable than those of the wild-type parent virus (Read & Frenkel, 1983 ;Oroskar & Read, 1987;Kwong & Frenkel, 1987;Kwong et al, 1988).…”

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

“…First evidence of necrosis induced by herpesviruses was shown in HSV-2 infected cells as early as in 1978. It was demonstrated to result from the inhibition of the proteosynthesis [49]. In BoHV-1 infected cells, the cellular protein synthesis is shut off in part by the vhs tegument protein [76,95].…”

Herpesvirus Saimiri-induced Proteins in Lytically Infected Cells. I. Time-ordered Synthesis

“…Blocking experiments with translation inhibitors and especially the use of amino acid analogues (Honess & Roizman, 1974;Fenwick & Walker, 1978; have proved particularly helpful for futher characterization of early proteins which control the synthesis of proteins produced later in the cycle. The synthesis of late polypeptides may be controlled via regulatory proteins or simply via the amount of virus DNA available for transcription (Honess & Watson, 1977a;Wolf & Roizman, 1978;Wolf & Bayliss, 1979).…”