Translational control of viral and host protein synthesis during the course of herpes simplex virus type 1 infection: evidence that initiation of translation is the limiting step.
Herpes simplex virus type 1 (HSV-1) infection induces the selective shut-off of host protein synthesis, other than ribosomal proteins, and the successive synthesis of viral proteins. Because viral mRNAs persist in the cytoplasm after viral protein synthesis has been inhibited, we hypothesized that viral gene expression may be under translational control. Expression of genes encoding immediate early ICP27, early DBP and late US11 proteins, together with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was monitored over the course of infection at the level of mRNA and protein synthesis. After an efficient synthesis beginning with the appearance of successive viral mRNAs in the cytoplasm, synthesis of viral proteins was shut off similarly to the synthesis of GAPDH. This shut-off was not achieved by mRNA degradation but by progressive shifts of viral mRNAs from large polyribosomes to smaller ones, then to 40S ribosomal subunits. Transient expression of the UL41 gene alone, directing synthesis of virion-associated host shut-off (VHS) protein, induced efficient mRNA degradation, but did not impair recruitment of the remaining GAPDH and beta-actin mRNAs into polyribosomes. These results indicate that HSV-1 induces a selective repression of initiation of mRNA translation which is probably the main cause of the shut-off of viral protein synthesis, and which contributes to the repression of host protein synthesis. VHS protein is not directly involved in this repression, at least in the absence of other viral proteins.
Laurent
A M
AM
Immuno-Virologie Moléculaire et Cellulaire CNRS UMR 5537, Faculté de Médecine Lyon-R.T.H. Laennec, Lyon, France.
Madjar
J J
JJ
Greco
A
A
D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases