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GTPases，对多种RNA和DNA病毒具有广泛的抗病毒活性。我们先前证明了猪Mx1蛋白（poMx1）抑制了经典猪瘟病毒（CSFV）（一种在经济上很重要的瘟病毒）的复制，而Mx1鼠标也是如此。未知为什么细胞核定位小鼠Mx1会抑制在细胞质中发生的CSFV复制。最后，我们评估了野生型小鼠Mx1和七个先前报道的突变体（K49A，G83R，A222V，A516V，G540E，R614E和ΔL4）的抗CSFV作用，并确定了R614E作用对抗CSFV复制的分子机制。一系列实验表明，mmMx1（R614E）突变体重新定位到细胞质并与CSFV核衣壳蛋白（Core）相互作用，从而抑制了病毒复制。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在物种之间的相对保守是广谱抗病毒特性的基础。