Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs.

Abstract

The herpes simplex virus viion contains a function that mediates the shutoff of host-protein synthesis and the degradation of host mRNA. Viral mutants affected in this function (vhs mutants) have previously been derived. Cells infected with these mutants exhibit a more stable synthesis of host as well as the immediate early (a)-viral proteins. We now show that a function associated with purified virions of the wild-type virus reduces the half-life of host and a mRNAs, whereas purified vhs-I mutant virions lack this activity. The functional half-life of many early ((3)-and late (y)-viral mRNAs is also prolonged in mutant virus infections. These studies suggest that the wild-type virion brings into cells a function that indiscrininately reduces the half-life of both host and viral transcripts and that the early translational shutoff of the host is a consequence of this function. This function may facilitate rapid transitions in the expression of groups of genes that are transcriptionally turned on at different times after infection.Cells infected with herpes simplex viruses 1 and 2 proceed through the sequential transcription of several coordinately regulated groups of viral genes, including the a (immediate early), A3 (delayed early), and yj and y2 (late) genes (1-3). As suggested originally by Honess and Roizman (1), this transcriptional regulation must also be accompanied by a negative translational-regulatory scheme. Thus, the translation of host mRNA is turned off soon after virus entry into the cells, and the synthesis of a-and (3-viral polypeptides decreases at later intervals after infection.The early shutoff of host-protein synthesis (4) (15). Surprisingly, the vhs mutants are also altered with respect to a function that is present in the wild-type (wt) virus inoculum, which decreases the synthesis of a proteins from preexisting a mRNA (15). These findings suggest that a single virion-associated function might limit the translation of both host and a mRNAs.In this paper, we present data concerning the specificity of the host shutofffunction. We show that purified virions of the wt virus, but not those of the vhs-i mutant virus, carry a function that reduces the half-life of host and a mRNAs.Furthermore, the functional half-life of many (-and y-viral mRNAs is also prolonged in vhs-i-infected cells. These findings suggest that wt virions contain a function that indiscriminately reduces the half-life of the majority of infected-cell mRNAs. EXPERIMENTAL PROCEDURESCells and Viruses. Mouse Ltk-cells were obtained from B. Roizman (University of Chicago) and Vero monkey cells were obtained from S. Bachenheimer (University of North Carolina). The derivation of the vhs-i mutant was described previously (15). Virus stocks representing cell lysates were prepared by three cycles of freeze-thawing of infected cells (16), and virions were purified in dextran T 10 gradients (17,18).Drug Treatment and Analyses of Proteins. For cycloheximide reversal in the presence of actinomycin D (1), the cells were incubated fo...

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

“…In BoHV-1 infected cells, the cellular protein synthesis is shut off in part by the vhs tegument protein [76,95]. By analogy to the HSV-1 UL41 encoded protein, the latter is supposed to degrade mRNA preexisting in the target cell [48,99]. Several studies were devoted to the regulation of apoptosis during productive BoHV-1 infection.…”

Degradation of cellular mRNA during influenza virus infection: its possible role in protein synthesis shutoff

“…How would viral m R N A s escape such a general m R N A degradation? The available data suggest that viral m R N A stability is rather limited: the half-life of both M1 and M2 m R N A s is 2.7 h (Valcfircel et al, 1991) and the kinetics of viral m R N A accumulation in infection indicate a similar stability for many of them (Hatada et al, 1989; and viral mRNAs, much in the way proposed for herpes simplex virus (Kwong & Frenkel, 1987;Kwong et al, 1988).…”

Comparative DNA sequence analysis of the host shutoff genes of different strains of herpes simplex virus: type 2 strain HG52 encodes a truncated UL41 product

“…This process is brought about by the direct or indirect action of a component of the virus particle which has been shown to be encoded by gene UL41 (Nishioka & Silverstein, 1978;Fenwick & Walker, 1978;Kwong et al, 1988;Fenwick & Everett, 1990). The consequence of UL41 function is a general destabilization of all host and viral mRNAs, resulting in preferential synthesis of viral proteins because of the more rapid synthesis of their messages (Stenberg & Pizer, 1982;Fenwick & McMenamin, 1984;Schek & Bachenheimer, 1985;Oroskar & Read, 1987, 1989Kwong & Frenkel, 1987). The efficiency of the shutoff process varies between different strains of virus.…”