The CRM1-dependent NES257−266 motif in the matrix protein: another factor influencing Newcastle disease virus propagation and virulence

作者：Yaodong Zhang, Jun Dai, Lei Tan, Daoe Mu, Ziyan Zhang, Cuiping Song, Yang Qu, Ning Tang, Ying Liao, Chan Ding, Yingjie Sun, Xusheng Qiu · 发表于：Veterinary Research · 年份：2025 · DOI：10.1186/s13567-025-01552-6 · 被引用次数：3 · 研究领域：Virology and Viral Diseases、Vector-Borne Animal Diseases、Mosquito-borne diseases and control

Abstract As an important structural protein of Newcastle disease virus (NDV), the M protein plays a crucial role in the assembly and budding of the virus. In previous reports, we confirmed the existence of a classical nuclear export signal (NES) sequence on the M protein (i.e . , amino acids 257 to 266), which plays an important role in the nuclear export of the protein. In this study, we found that the NES 257−266 motif is associated with the evolutionary history of NDV, and found that the NES-mediated nuclear export efficiency of M proteins varies among different genotypes. Further research on the LaSota-NES and JSD0812-NES variants showed that the NES both affects the nuclear-cytoplasmic trafficking efficiency of M protein and influences the formation of virus-like particles (VLPs). The NES 257−266 conforms to the chromosome region maintenance 1 (CRM1)-associated consensus leucine/isoleucine-rich NES motif, and our results confirm that the NES-mediated nuclear-cytoplasmic trafficking of M protein is dependent on the CRM1 pathway. At last, several recombinant LaSota strains were rescued using reverse genetics, with their NES sequence replaced by either a potent NES motif, or an R247K mutation, or both. The rescued rLaSota-QMS and rLaSota-FM strains showed elevated hemagglutination (HA) titers, increased 50% egg infective dose (EID 50 ) values, along with marginally higher mean death time (MDT) and intracerebral pathogenicity index (ICPI) values, all of which are attributabl...