Studies with mutant viruses have suggested that the product of gene UL41 of herpes simplex virus type 1 (HSV-1) controls the virion-mediated inhibition of cellular protein synthesis as well as the rate of degradation of viral mRNAs. HSV-1 strain 17+ has a weak host shutoff function, whereas HSV-2 strain G shuts off strongly. A gene of HSV-2(G), judged from its position in the genome to be the probable analogue of gene UL41 of HSV-1, was inserted into the nonessential thymidine kinase gene of HSV-1(17+). The recombinant virus, 17G41, exhibited a strong shutoff function and its immediate early mRNA did not accumulate in the presence of cycloheximide. It resembled HSV-2(G) in these respects and not the parent, confirming the function of the transferred gene. Recombinant virus 17G41 carries the UL41 genes of both strains, 17+ and G, and in this situation the strong shutoff function was dominant. However, after mixed infection with equal multiplicities of 17G41 and HSV- 1(17+) the weak shutoff function was dominant. The recombinant, 17G41, was further modified by insertion of a lacZ expression cassette into the coding region of the original gene UL41 (17+). The resulting virus, 17(41−)G41, also had a strong shutoff activity but grew poorly in tissue culture.
BrownS. M.,
RitchieD. A.,
Subak-SharpeJ. H.1973; Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. Journal of General Virology 18:329–346
EjercitoP. M.,
KieffE. D.,
RoizmanB.1968; Characterization of HSV strains differing in their effect on social behavior of infected cells. Journal of Virology 2:357–364
FenwickM. L.,
ClarkJ.1982; Expression of early viral genes: a possible pre-alpha protein in cells infected with HSV. Biochemical and Biophysical Research Communications 108:1454–1459
FenwickM. L.,
ClarkJ.1983; The effect of cycloheximide on the accumulation and stability of functional α-mRNA in cells infected with herpes simplex virus. Journal of General Virology 64:1955–1963
FenwickM. L.,
McmenaminM. M.1984; Early virion-associated suppression of cellular protein synthesis is accompanied by inactivation of mRNA. Journal of General Virology 65:1225–1228
FenwickM. L.,
OwenS. A.1988; On the control of immediate early (α) mRNA survival in cells infected with herpes simplex virus. Journal of General Virology 69:2869–2877
GallowayD. A.,
NelsonJ. A.,
McdougallJ. K.1984; Small fragments of herpesvirus DNA with transforming activity contain insertion sequence-like structures. Proceedings of the National Academy of Sciences, U.S.A 81:4736–4740
HillT. M.,
SadlerJ. R.,
BetzJ. L.1985; Virion component of HSV-1 (KOS) interferes with early shutoff of host protein synthesis induced by HSV-2 (186). Journal of Virology 56:312–316
KwongA. D.,
FrenkelN.1987; HSV-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proceedings of the National Academy of Sciences, U.S.A 84:1926–1930
McgeochD. J.,
DalrympleM. A.,
DavisonA. J.,
DolanA.,
FrameM. C.,
McnabD.,
PerryL. J.,
ScottJ. E.,
TaylorP.1988; The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:1531–1574
MorseL. S.,
PereiraL.,
RoizmanB.,
SchafferP. A.1978; Anatomy of HSV DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 x HSV-2 recombinants. Journal of Virology 26:389–410
NishiokaY.,
SilverstienS.1978; Requirement of protein synthesis for the degradation of host mRNA in FL cells infected with HSV-1. Journal of Virology 27:619–627
ReadG. S.,
FrenkelN.1983; HSV mutants defective in the virion-associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of alpha (IE) viral polypeptides. Journal of Virology 46:498–512
RigbyP. W. J.,
DieckmannM.,
RhodesC.,
BergP.1977; Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. Journal of Molecular Biology 113:237–251
SchekN.,
BachenheimerS. L.1985; Degradation of cellular mRNAs induced by a virion-associated factor during HSV infection of Vero cells. Journal of Virology 55:601–610
StowN. D.,
WilkieN. M.1976; An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA. Journal of General Virology 33:447–458
StowN. D.,
McmonagleE. C.,
DavisonA. J.1983; Fragments from both termini of HSV-1 genome contain signals required for the encapsidation of viral DNA. Nucleic Acids Research 11:8205–8220
WilkieN. M.,
ClementsJ. B.,
BollW.,
LonsdaleD.,
WeissmannC.1979; Hybrid plasmids containing an active thymidine kinase gene of HSV-1. Nucleic Acids Research 7:859–877