MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
Vet Microbiol. 2020 Apr;243:108621. doi: 10.1016/j.vetmic.2020.108621. Epub 2020 Feb 26.
Mx proteins are interferon-induced GTPases that have broad antiviral activity against a wide range of RNA and DNA viruses. We previously demonstrated that porcine Mx1 protein (poMx1) inhibited the replication of classical swine fever virus (CSFV), an economically important Pestivirus, and that mouse Mx1 did so as well. It is unknown why the nucleus-localizing mouse Mx1 inhibits CSFV replication which occurs in the cytoplasm. To the end, we assessed the anti-CSFV actions of wild type mouse Mx1 and seven previously reported mutants (K49A, G83R, A222V, A516V, G540E, R614E and ΔL4) and identified the molecular mechanism of R614E action against CSFV replication. A series of experiments revealed that mmMx1 (R614E) mutant reposted to the cytoplasm and interacted with the CSFV nucleocapsid protein (Core), thereby inhibiting viral replication. These findings broaden our understanding of the function of Mx protein family members against CSFV and suggest that the relative conservation of Mx1 among species is the basis of broad-spectrum antiviral properties.
Mx 蛋白是干扰素诱导的 GTPase，对广泛的 RNA 和 DNA 病毒具有广泛的抗病毒活性。我们之前证明，猪 Mx1 蛋白（poMx1）抑制了经典猪瘟病毒（CSFV）的复制，CSFV 是一种具有重要经济意义的瘟病毒，而鼠 Mx1 也具有这种作用。目前尚不清楚为什么定位于细胞核的鼠 Mx1 会抑制发生在细胞质中的 CSFV 复制。为此，我们评估了野生型鼠 Mx1 及其之前报道的七种突变体（K49A、G83R、A222V、A516V、G540E、R614E 和 ΔL4）对 CSFV 的抗病毒作用，并确定了 R614E 抑制 CSFV 复制的分子机制。一系列实验表明，mmMx1（R614E）突变体重新定位于细胞质并与 CSFV 核衣壳蛋白（Core）相互作用，从而抑制病毒复制。这些发现拓宽了我们对 Mx 蛋白家族成员针对 CSFV 的功能的理解，并表明 Mx1 在物种间的相对保守性是广谱抗病毒特性的基础。
