A Conserved peptide in West Nile virus NS4A protein contributes to proteolytic processing and is essential for replication

Abstract

The West Nile virus strain Kunjin virus (WNV KUN) NS4A protein is a multifunctional protein involved in membrane proliferation, stimulation of cellular pathways, and evasion of host defense and is a major component of the WNV KUN RNA replication complex. We identified a highly conserved region ( 120P-E-P-E 123) upstream of the viral protease dibasic cleavage site and investigated whether this motif was required for WNV KUN replication. Single point mutations to alanine and a PEPE deletion mutation were created in a full-length infectious WNV KUN molecular clone. All mutations drastically impaired viral replication and virion production, except that of the P122A mutant, which was slightly att..