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

文献类型： 外文期刊

第一作者： Zhang, Yaodong

作者： Zhang, Yaodong;Tan, Lei;Mu, Daoe;Zhang, Ziyan;Song, Cuiping;Qu, Yang;Tang, Ning;Liao, Ying;Ding, Chan;Sun, Yingjie;Qiu, Xusheng;Dai, Jun;Ding, Chan

作者机构：

关键词： Newcastle disease virus; M protein; NES; CRM1; replication; virulence

期刊名称：VETERINARY RESEARCH （ 影响因子：3.5； 五年影响因子：4.0 ）

ISSN： 0928-4249

年卷期： 2025 年 56 卷 1 期

页码：

收录情况： SCI

摘要： 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 NES257-266 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 NES257-266 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 (EID50) values, along with marginally higher mean death time (MDT) and intracerebral pathogenicity index (ICPI) values, all of which are attributable to their enhanced proliferation rates when compared to the wild-type (wt) rLaSota strain. Our findings contribute to a better understanding of the molecular mechanisms of replication and pathogenicity in NDV and, by extension, in other paramyxoviruses.

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