cis expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor
cis expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor
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DOI：
10.1128/jvi.75.24.12028-12038.2001
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发表时间：
2001-12-01
影响因子：
5.4
通讯作者：
Doms, RW
中科院分区：
文献类型：
--
作者：
Lee, B;Leslie, G;Doms, RW
DC-SIGN是一种在体内树突状细胞和限制性巨噬细胞群上表达的C型凝集素，其结合gp 120并反式作用以使T细胞能够被人类免疫缺陷病毒1型（HIV-1）有效感染。我们在这里报告，DC-SIGN，当表达在顺式与CD 4和辅助受体，允许更有效的感染艾滋病毒和猴免疫缺陷病毒（SIV）株，虽然程度从2到40倍不等，这取决于病毒株。DC-SIGN在靶细胞上的表达并没有减轻病毒进入对CD 4或辅助受体的需求。DC-SIGN在多个淋巴系上的稳定表达使得R5 X4和X4病毒能够更有效地进入和复制。因此，与亲本细胞系相比，在DC-SIGN转导的Jurkat细胞中实现生产性复制分别需要10倍和100倍的89.6（R5/X4）和NL 4 -3（X4）。此外，表达非常低水平的CCR 5的T细胞系上的DC-SIGN表达使得R5病毒能够以CCR 5依赖性方式进入和复制，这是亲本细胞系所不表现出的特性。因此，DC-SIGN表达可以促进顺式病毒感染，并且可以扩大病毒嗜性而不影响辅助受体偏好。此外，DC-SIGN的共表达使一些病毒能够使用替代的共受体如STRL 33来感染细胞，而在其不存在的情况下，未观察到感染。免疫组织化学和共聚焦显微镜数据表明，DC-SIGN共表达和共定位与CD 4和CCR 5对肺泡巨噬细胞，强调这些顺式增强效应的生理意义。
DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 and acts in trans to enable efficient infection of T cells by human immunodeficiency virus type 1 (HIV-1). We report here that DC-SIGN, when expressed in cis with CD4 and coreceptors, allowed more efficient infection by both HIV and simian immunodeficiency virus (SIV) strains, although the extent varied from 2- to 40-fold, depending on the virus strain. Expression of DC-SIGN on target cells did not alleviate the requirement for CD4 or coreceptor for viral entry. Stable expression of DC-SIGN on multiple lymphoid lines enabled more efficient entry and replication of R5X4 and X4 viruses. Thus, 10- and 100-fold less 89.6 (R5/X4) and NL4-3 (X4), respectively, were required to achieve productive replication in DC-SIGN-transduced Jurkat cells when compared to the parental cell line. In addition, DC-SIGN expression on T-cell lines that express very low levels of CCR5 enabled entry and replication of R5 viruses in a CCR5-dependent manner, a property not exhibited by the parental cell lines. Therefore, DC-SIGN expression can boost virus infection in cis and can expand viral tropism without affecting coreceptor preference. In addition, coexpression of DC-SIGN enabled some viruses to use alternate coreceptors like STRL33 to infect cells, whereas in its absence, infection was not observed. Immunohistochemical and confocal microscopy data indicated that DC-SIGN was coexpressed and colocalized with CD4 and CCR5 on alveolar macrophages, underscoring the physiological significance of these cis enhancement effects.