Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load

For double-stranded RNA (dsRNA) to signal the presence of foreign (non-self ) nucleic acid, self-RNA-self-RNA interactions should be minimized. Indeed, self-RNAs appear to have been fine-tuned over evolutionary time by the int roduction of purines in clusters in the loop regions of stem-loop structure s. This adaptation should militate against the "kissing" interactions which initiate formation of dsRNA. Our analyses of virus base compositions sugge st that, to avoid triggering the host cell's dsRNA surveillance mechanism, most viruses purine-load their RNAs to resemble host RNAs ("stealth" strate gy). However, some GC-rich latent viruses (HTLV-I, EBV) pyrimidine-load the ir RNAs. It is suggested that when virus production begins, these RNAs sudd enly increase in concentration and impair host mRNA function by virtue of a n excess of complementary "kissing" interactions ("surprise" strategy). Rem arkably, the only mRNA expressed in the most fundamental form of EBV latenc y (the "EBNA-1 program") is purine-loaded. This apparent stealth strategy i s reinforced by a simple sequence repeat which prefers purine-rich codons. During latent infection the EBNA-1 protein may evade recognition by cytotox ic T-cells, not by virtue of containing a simple sequence amino acid repeat as has been proposed, but by virtue of the encoding mRNA being purine-load ed to prevent interactions with host RNAs of either genic or non-genic orig in. (C) 2001 Academic Press.