Channel-Inactivating Mutations and Their Revertant Mutants in the Envelope Protein of Infectious Bronchitis Virus.

摘要: It has been shown previously in the severe acute respiratory syndrome coronavirus (SARS-CoV) that two point mutations, N15A and V25F, transmembrane domain (TMD) of envelope (E) protein abolished channel activity led to vivo attenuation. Pathogenicity was recovered mutants also regained E activity. In particular, V25F rapidly compensated by changes at multiple V25F-facing TMD residues located on a neighboring monomer, consistent with recovery oligomerization. Here, we show using infected cells same T16A A26F, gamma-CoV infectious bronchitis virus (IBV) lead to, principle, similar results. However, IBV A26F did not abolish oligomer formation mutations N- C-terminal extramembrane domains (EMDs). The EMD clustered along an insertion sequence specific gamma-CoVs. Nuclear magnetic resonance data are presence only one E, suggesting fitness these revertant is through allosteric interaction between EMDs TMD. present results important for development live attenuated vaccines when channel-inactivating introduced protein.IMPORTANCE ion SARS-CoV determinant virulence, abolishment leads viral deletion may be strategy generating but can trigger undesirable compensatory mechanisms modifications other proteins regain virulence. Therefore, more suitable approach introduce small critical attenuating mutations. For this, stability should examined understand reversion. avian recombinant system deficient release restored Unexpectedly, most appeared domains, particularly gammacoronaviruses. Our structural propose single domains.