YLMY Tyrosine Residue within the Cytoplasmic Tail of Newcastle Disease Virus Fusion Protein Regulates Its Surface Expression to Modulate Viral Budding and Pathogenicity.
YLMY Tyrosine Residue within the Cytoplasmic Tail of Newcastle Disease Virus Fusion Protein Regulates Its Surface Expression to Modulate Viral Budding and Pathogenicity.
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DOI：
10.1128/spectrum.02173-21
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发表时间：
2021-12-22
影响因子：
3.7
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Bu Y;Teng Q;Feng D;Sun L;Xue J;Zhang G
纽卡斯尔病毒（NDV）融合蛋白介导NDV的融合活性，是NDV致病性的决定因素。已知F蛋白的胞外域对融合具有重大影响，并且一些报道还表明胞质尾区（CT）在病毒进入、F蛋白切割和融合中的作用，其由特定基序调节。我们发现一个高度保守的酪氨酸残基位于YLMY基序。524和527位的酪氨酸残基在病毒复制和致病性中具有不同的作用，并且与F蛋白的细胞内加工相关。酪氨酸残基突变体影响F蛋白从内质网到高尔基体的运输，导致不同的切割效率。F蛋白随后被转运到细胞表面，在那里它参与病毒出芽，这是一个与酪氨酸残基引起的致病性差异密切相关的过程。此外，不同的突变都导致低融合表型。我们认为YLMY基序的高度保守的酪氨酸残基使用与基于酪氨酸的基序（YXXΦ）类似的机制来调节F蛋白转运，从而影响病毒复制和致病性。副粘病毒融合糖蛋白的氨基端胞质结构域包括影响蛋白质加工和细胞表面表达的运输信号。本研究阐明了F蛋白胞质区YLMY基序中不同位置的酪氨酸残基调节F蛋白的转运，从而影响病毒的复制和致病性。这项研究增加了我们对NDV毒力如何由F蛋白介导的理解，并为CT在病毒生命周期中的作用提供了新的视角。这一信息可能是有用的NDV作为一种有效的疫苗载体和溶瘤剂的发展。
Newcastle disease virus (NDV) fusion protein mediates the virus’s fusion activity, which is a determinant of NDV pathogenicity. The ectodomain of the F protein is known to have a major impact on fusion, and several reports have also indicated the role of the cytoplasmic tail (CT) in viral entry, F protein cleavage, and fusion, which are regulated by specific motifs. We found a highly conserved tyrosine residue located in the YLMY motif. The tyrosine residues at positions 524 and 527 have different roles in viral replication and pathogenicity and are associated with F protein intracellular processing. Tyrosine residues mutants affect the transportation of the F protein from the endoplasmic reticulum to the Golgi apparatus, resulting in different cleavage efficiencies. F protein is subsequently transported to the cell surface where it participates in viral budding, a process closely related to the distinctions in pathogenicity caused by the tyrosine residues. In addition, the different mutations all led to a hypofusogenic phenotype. We believe that the highly conserved tyrosine residue of the YLMY motif uses a similar mechanism to the tyrosine-based motif (YXXΦ) to regulate F protein transport and thus affect viral replication and pathogenicity. IMPORTANCE The amino-terminal cytoplasmic domains of paramyxovirus fusion glycoproteins include trafficking signals that influence protein processing and cell surface expression. This study clarified that tyrosine residues at different positions in the YLMY motif in the cytoplasmic region of the F protein regulate F protein transportation, thereby affecting viral replication and pathogenicity. This study has increased our understanding of how NDV virulence is mediated by the F protein and provides a fresh perspective on the role of CT in the virus’s life cycle. This information may be useful in the development of NDV as an effective vaccine vector and oncolytic agent.
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