Herpes simplex virus 1716, an ICP 34.5 null mutant, is unable to replicate in CV-1 cells due to a translational block that can be overcome by coinfection with SV40.
Herpes simplex virus (HSV) mutants lacking the gene encoding infected cell protein (ICP) 34.5 exhibit an attenuated phenotype in models of pathogenesis and have been used for experimental cancer therapy. Recently it was shown that the HSV ICP 34.5 protein functions to prevent the host cell-induced double-stranded RNA-activated protein kinase (PKR)-dependent translational block that normally occurs during virus infection. We now report that an HSV ICP 34.5 mutant called HSV-1716 is unable to replicate in the simian kidney cell-derived line CV-1, due to a translational block. Moreover, we find that this block can be overcome by simian virus 40 (SV40). This has been shown directly by infecting CV-1 cells with SV40 and HSV-1716 simultaneously, and indirectly via HSV-1716 infection of COS-1 cells (CV-1 cells transformed by an origin-defective mutant of SV40 that codes for wild-type T antigen). The translational block is restored when infections are done in the presence of the phosphatase inhibitor okadaic acid. These results support, but do not directly prove, contentions that HSV ICP 34.5 interacts with the PKR pathway to restore translation in non-permissive cells, and that SV40 large T antigen has a similar functional role, but acts downstream of the site of ICP 34.5 interaction (eIF2alpha) in the pathway. Study of this CV-1/COS-1 system should allow further clarification of the virus-host interactions that underlie the restricted replication of HSV-1 ICP 34.5 gene null mutants.
Randazzo
B P
BP
The Wistar Institute, Philadelphia, PA 19104, USA.
Tal-Singer
R
R
Zabolotny
J M
JM
Kesari
S
S
Fraser
N W
NW
D000818:Animals; D002460:Cell Line; D000882:Haplorhini; D009154:Mutation; D014176:Protein Biosynthesis; D013539:Simian virus 40 / Q000502:physiology*; D018139:Simplexvirus / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1