During the initial
infection of B lymphocytes by Epstein-Barr virus (EBV) only a few viral genes are expressed, six of which encode the
EBV nuclear antigens, EBNAs 1-6. The majority of EBNA mRNAs share common 5'-ends containing a variable number of two alternating and repeated exons transcribed from the BamHI W major internal repeats of the
viral DNA. These sequences can also exist as independent small
RNA species in some EBV-infected cell types. We present evidence that transcripts from these W repeat regions can exert a trans-acting effect on
protein synthesis, through their ability to activate the dsRNA-dependent
protein kinase PKR. UV cross-linking and filter binding assays have demonstrated that the W transcripts bind specifically to PKR and can compete with another EBV-encoded small
RNA,
EBER-1, which was shown previously to bind this
kinase. In the reticulocyte lysate system the W RNAs shut off
protein synthesis through an ability to activate PKR. In contrast to
EBER-1, the W RNAs are unable to block the dsRNA-dependent activation of PKR. Using a purified preparation of the
protein kinase we have shown that the W transcripts directly activate PKR in vitro. The results suggest that EBV has the ability both to activate and to inhibit PKR through the actions of different products of viral transcription.