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 sh ut-off of host protein synthesis, other than ribosomal proteins, and t he 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 co ntrol. Expression of genes encoding immediate early ICP27, early DBP a nd late US11 proteins, together with glyceraldehyde-3-phosphate dehydr ogenase (GAPDH), was monitored over the course of infection at the lev el of mRNA and protein synthesis. After an efficient synthesis beginni ng with the appearance of successive viral mRNAs in the cytoplasm, syn thesis of viral proteins was shut off similarly to the synthesis of GA PDH, This shut-off was not achieved by mRNA degradation but by progres sive shifts of viral mRNAs from large polyribosomes to smaller ones, t hen to 405 ribosomal subunits, Transient expression of the UL41 gene a lone, directing synthesis of virion-associated host shut-off (VHS) pro tein, induced efficient mRNA degradation, but did not impair recruitme nt of the remaining GAPDH and p-actin mRNAs into polyribosomes, These results indicate that HSV-1 induces a selective repression of initiati on of mRNA translation which is probably the main cause of the shut-of f of viral protein synthesis, and which contributes to the repression of host protein synthesis. VHS protein is not directly involved in thi s repression, at least in the absence of other viral proteins.