The α2,3-sialyltransferase encoded by myxoma virus is a virulence factor that contributes to immunosuppression.
The α2,3-sialyltransferase encoded by myxoma virus is a virulence factor that contributes to immunosuppression.
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DOI：
10.1371/journal.pone.0118806
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gillet L
中科院分区：
文献类型：
--
作者：
Boutard B;Vankerckhove S;Markine-Goriaynoff N;Sarlet M;Desmecht D;McFadden G;Vanderplasschen A;Gillet L
粘液瘤病毒（MYXV）在欧洲兔子中诱导一种称为粘液瘤病的致命疾病。MYXV是通过其M138 L基因编码α 2，3-唾液酸转移酶的罕见病毒之一。在这项研究中，我们表明，虽然酶的情况下是不相关的任何在体外赤字，M138 L缺陷株是高度减毒的体内。事实上，虽然所有感染亲本和回复突变株的兔在感染后9天内死于严重的粘液瘤病，但除一只接种M138 L缺陷株的兔外，所有兔均在感染后存活。在原发性病变中，这种对感染的抵抗力与先天免疫细胞（主要是中性粒细胞）在感染后4天迁移到病毒复制部位的能力增加有关。这之后是针对MYXV的更好的特异性免疫应答的发展。事实上，在感染后第9天，我们观察到M138 L敲除感染后淋巴结中淋巴细胞的重要增殖和血管的强烈充血。因此，在这些家兔中，我们观察到在原发性病变的整个真皮中有强烈的单核细胞浸润和较高滴度的中和抗体。最后，这种适应性免疫应答为这些存活的兔提供了保护，使其免受MYXV WT菌株的攻击。总之，这些结果表明，M138 L基因的表达直接或间接有助于MYXV的免疫逃避。在未来，这些结果可以帮助我们更好地了解多发性粘液瘤病的发病机制，以及聚糖在调节免疫反应中的重要性。
Myxoma virus (MYXV) induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an α2,3-sialyltransferase through its M138L gene. In this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the M138L deficient strains are highly attenuated in vivo. Indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one rabbit inoculated with the M138L deficient strains survived the infection. In primary lesions, this resistance to the infection was associated with an increased ability of innate immune cells, mostly neutrophils, to migrate to the site of virus replication at 4 days post-infection. This was followed by the development of a better specific immune response against MYXV. Indeed, at day 9 post-infection, we observed an important proliferation of lymphocytes and an intense congestion of blood vessels in lymph nodes after M138L knockouts infection. Accordingly, in these rabbits, we observed an intense mononuclear cell infiltration throughout the dermis in primary lesions and higher titers of neutralizing antibodies. Finally, this adaptive immune response provided protection to these surviving rabbits against a challenge with the MYXV WT strain. Altogether, these results show that expression of the M138L gene contributes directly or indirectly to immune evasion by MYXV. In the future, these results could help us to better understand the pathogenesis of myxomatosis but also the importance of glycans in regulation of immune responses.
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影响因子：
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通讯作者：
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