THE RNA-BINDING AND EFFECTOR DOMAINS OF THE VIRAL NS1 PROTEIN ARE CONSERVED TO DIFFERENT EXTENTS AMONG INFLUENZA-A AND INFLUENZA-B VIRUSES

The NS1 protein of the influenza A/Udorn/72 virus possesses two import ant functional domains: an RNA-binding domain near the amino-terminal end and an effector domain in the carboxyl half of the molecule. Thoug h the NS1 proteins of influenza A and B viruses share little sequence homology, an RNA-binding domain with the same activities is preserved in the NS1 protein of influenza B/Lee/40 virus. The RNA-binding domain s of the NS1 proteins of these influenza A and a viruses share the fol lowing properties: (i) they specifically bind to the same three RNA ta rgets, poly(A), U6 snRNA, and double-stranded (ds) RNA; (ii) a polypep tide containing an amino-terminal sequence of the protein possesses al l the RNA-binding activity of the full-length protein and exists in th e form of a dimer; (iii) the binding to U6 snRNA causes an inhibition of pre-mRNA splicing in vitro; and (iv) the binding to dsRNA blocks th e activation of the PKR kinase in vitro. The conservation of the RNA-b inding domain of the NS1 protein among influenza A and B viruses stron gly suggests that this domain is required for the replication of all t hese influenza viruses. In contrast, the NS1 protein of influenza B vi rus (NS1B protein) lacks an effector domain that functions like that o f the NS1 protein of influenza A virus (NS1A protein). The effector do main of the NS1A protein is required for two of its in vivo activities : the inhibition of the nuclear export of poly(A)-containing mRNA and the inhibition of pre-mRNA splicing. The NS1B protein lacks these two in vivo activities, In addition, a naturally occuring, truncated NS1A protein lacks such an effector domain. Consequently, an effector domai n that functions like that of full-length NS1A proteins is not absolut ely required for the replication of influenza A and B viruses. We disc uss the implications of these results for the roles of the RNA-binding and effector domains of the NS1 protein during infection by influenza A and B viruses. (C) 1996 Academic Press, Inc.