DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses
DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses
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DOI：
10.1128/jvi.77.22.12022-12032.2003
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Ryman, KD
中科院分区：
文献类型：
--
作者：
Klimstra, WB;Nangle, EM;Ryman, KD
C型凝集素，如DC-SIGN和L-SIGN，结合宿主和病原体蛋白的甘露糖修饰，已被证明与几种病毒的糖蛋白结合，促进顺式或反式感染。DC-SIGN和L-SIGN表达于虫媒病毒感染的几个早期靶点，包括树突状细胞(DC)和网状内皮系统的细胞。在本研究中，我们发现DC-SIGN和L-SIGN可以作为甲型病毒属虫媒病毒Sindbis(SB)的附着受体。稳定转染DC-SIGN或L-SIGN的人单核细胞THP-1细胞对SB病毒复制是允许的，而未转染组基本上是不允许的。当通过电穿孔病毒转录物消除附着和进入步骤时，大多数对照THP-1细胞是允许的。表达DC-SIGN/L SIGN的细胞的感染性可被酵母甘露聚糖、乙二胺四乙酸乙二酯或DC-SIGN/L-SIGN特异性单抗阻断。原代人类DC感染SB病毒也依赖于相似标准的SIGN表达。此外，在限制复杂碳水化合物含量的条件下，在C6/36蚊子细胞或CHO哺乳动物细胞中产生病毒颗粒，大大增加了SB病毒与表达这些凝集素的THP-1细胞的结合和感染。C6/36来源的病毒对原代人类DC的传染性也比CHO来源的病毒高得多。这些结果表明：(1)DC-SIGN和L-SIGN等凝集素分子可能是节肢动物传播病毒的共同附着受体分子；(2)节肢动物载体产生和传递的虫媒病毒颗粒可能优先靶向携带这些或类似凝集素分子的脊椎动物宿主细胞；(3)已鉴定出一种能够复制甲型病毒但缺乏附着受体的细胞系。
C-type lectins such as DC-SIGN and L-SIGN, which bind mannose-enriched carbohydrate modifications of host and pathogen proteins, have been shown to bind glycoproteins of several viruses and facilitate either cis or trans infection. DC-SIGN and L-SIGN are expressed in several early targets of arbovirus infection, including dendritic cells (DCs) and cells of the reticuloendothelial system. In the present study, we show that DC-SIGN and L-SIGN can function as attachment receptors for Sindbis (SB) virus, an arbovirus of the Alphavirus genus. Human monocytic THP-1 cells stably transfected with DC-SIGN or L-SIGN were permissive for SB virus replication, while untransfected controls were essentially nonpermissive. The majority of control THP-1 cells were permissive when attachment and entry steps were eliminated through electroporation of virus transcripts. Infectivity for the DC-SIGN/L-SIGN-expressing cells was largely blocked by yeast mannan, EDTA, or a DC-SIGN/L-SIGN-specific monoclonal antibody. Infection of primary human DCs by SB virus was also dependent upon SIGN expression by similar criteria. Furthermore, production of virus particles in either C6/36 mosquito cells or CHO mammalian cells under conditions that limited complex carbohydrate content greatly increased SB virus binding to and infection of THP-1 cells expressing these lectins. C6/36-derived virus also was much more infectious for primary human DCs than CHO-derived virus. These results suggest that (i) lectin molecules such as DC-SIGN and L-SIGN may represent common attachment receptor molecules for arthropod-borne viruses, (ii) arbovirus particles produced in and delivered by arthropod vectors may preferentially target vertebrate host cells bearing these or similar lectin molecules, and (iii) a cell line has been identified that can productively replicate alphaviruses but is deficient in attachment receptors.