The Influenza A Virus Protein NS1 Displays Structural Polymorphism

Abstract

NS1 of influenza A virus is a multifunctional protein associated with numerous strain-specific regulatory functions during viral infection, including conferring resistance to antiviral interferon induction, replication, pathogenesis, virulence, and host range. NS1 has two domains, an RNA-binding domain and an effector domain separated by a linker. To date, the only full-length NS1 structure available is that from an H5N1 strain (A/Vietnam/1203/2004). Here, we determined crystal structures of the wild type and a linker region mutant of the H6N6 NS1 (A/blue-winged teal/MN/993/1980), which together with the previously determined H5N1 NS1 structure show that NS1 exhibits significant strain-dependent structural polymorphism due to variations in linker length, residue composition at position 71, and a mechanical hinge. Such a structural polymorphism may be the basis for strain-specific functions associated with NS1.