The RNA-binding and effector domains of the viral NS1 protein are conserved to different extents among influenza A and B viruses.
The NS1 protein of the influenza A/Udorn/72 virus possesses two important functional domains: an RNA-binding domain near the amino-terminal end and an effector domain in the carboxyl half of the molecule. Though 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 domains of the NS1 proteins of these influenza A and B viruses share the following properties: (i) they specifically bind to the same three RNA targets, poly(A), U6 snRNA, and double-stranded (ds) RNA; (ii) a polypeptide containing an amino-terminal sequence of the protein possesses all the RNA-binding activity of the full-length protein and exists in the 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 the activation of the PKR kinase in vitro. The conservation of the RNA-binding domain of the NS1 protein among influenza A and B viruses strongly suggests that this domain is required for the replication of all these influenza viruses. In contrast, the NS1 protein of influenza B virus (NS1B protein) lacks an effector domain that functions like that of the NS1 protein of influenza A virus (NS1A protein). The effector domain 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 occurring, truncated NS1A protein lacks such an effector domain. Consequently, an effector domain that functions like that of full-length NS1A proteins is not absolutely required for the replication of influenza A and B viruses. We discuss 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.
Wang
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Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08855, USA.
Krug
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RM
D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D017124:Conserved Sequence; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D009981:Influenza B virus / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012322:RNA Precursors; D012326:RNA Splicing; D012330:RNA, Double-Stranded / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D019892:eIF-2 Kinase
C085820:INS1 protein, influenza virus; D012322:RNA Precursors; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017361:Viral Nonstructural Proteins; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase