Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.
Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.
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DOI：
10.1371/journal.pone.0060838
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Michelow IC
中科院分区：
文献类型：
--
作者：
Brudner M;Karpel M;Lear C;Chen L;Yantosca LM;Scully C;Sarraju A;Sokolovska A;Zariffard MR;Eisen DP;Mungall BA;Kotton DN;Omari A;Huang IC;Farzan M;Takahashi K;Stuart L;Stahl GL;Ezekowitz AB;Spear GT;Olinger GG;Schmidt EV;Michelow IC
甘露糖结合凝集素（MBL）是先天性免疫系统中识别病原体特异性表面聚糖的关键可溶性效应物。令人惊讶的是，可能使儿童和免疫功能低下的个体易患传染病的低产量MBL遗传变异在人群中比预期的更常见。由于某些免疫防御分子，如免疫球蛋白，可以利用入侵性病原体，我们假设MBL也可能在某些情况下增强感染。因此，在人群中常见的低和中等MBL水平可能是平衡选择的结果。使用假型和真实糖基化病毒的模型感染系统，我们证明了MBL确实在低补体条件下增强了埃博拉病毒、亨德拉病毒、尼帕病毒和西尼罗河病毒的感染。用埃博拉病毒（EBOV）糖蛋白假型慢病毒进行的机制研究证实，MBL通过MBL碳水化合物识别结构域以特异性方式结合病毒表面上的N-连接聚糖表位，这是增强感染所必需的。MBL介导EBOV的脂筏依赖性巨胞饮作用，与丝状病毒典型内吞途径相比，该途径似乎需要较少的肌动蛋白或早期内体加工。使用经验证的RNA干扰筛选，我们将C1 QBP（gC 1 qR）鉴定为介导MBL依赖性增强EBOV感染的候选表面受体。我们还鉴定了dectin-2（CLEC 6A）作为EBOV的潜在新候选附着因子。我们的研究结果支持先天免疫单倍型的概念，它代表MBL和补体成分C4基因之间的关键相互作用，并可能改变对某些糖基化病原体的易感性或抗性。因此，较高水平的天然或外源性MBL在相对低补体血症的情况下可能是有害的，这种相对低补体血症可能是遗传性的或由于活动性感染期间的免疫耗竭而发生的。我们的研究结果证实了我们的假设，即感染性疾病的压力可能部分导致了MBL突变单倍型的进化选择。
Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes.
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影响因子：
6.7
作者：
Gunn BM;Morrison TE;Whitmore AC;Blevins LK;Hueston L;Fraser RJ;Herrero LJ;Ramirez R;Smith PN;Mahalingam S;Heise MT
通讯作者：
Heise MT
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
DOI：
10.1016/s1473-3099(10)70166-3
发表时间：
2010-10
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Halstead SB;Mahalingam S;Marovich MA;Ubol S;Mosser DM
通讯作者：
Mosser DM
影响因子：
6.4
作者：
Catano, Gabriel;Agan, Brian K.;Ahuja, Sunil K.
通讯作者：
Ahuja, Sunil K.
影响因子：
6.4
作者：
de Messias-Reason, Iara J.;Boldt, Angelica B. W.;Kun, Juergen F. J.
通讯作者：
Kun, Juergen F. J.