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Novel Member of the CD209 (DC-SIGN) Gene Family in Primates

机译:灵长类动物中CD209(DC-SIGN)基因家族的新成员

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摘要

Two CD209 family genes identified in humans, CD209 (DC-SIGN) and CD209L (DC-SIGNR/L-SIGN), encode C-type lectins that serve as adhesion receptors for ICAM-2 and ICAM-3 and participate in the transmission of human and simian immunodeficiency viruses (HIV and SIV, respectively) to target cells in vitro. Here we characterize the CD209 gene family in nonhuman primates and show that recent evolutionary alterations have occurred in this family across primate species. All of the primate species tested, specifically, Old World monkeys (OWM) and apes, have orthologues of human CD209. In contrast, CD209L is missing in OWM but present in apes. A third family member, that we have named CD209L2, was cloned from rhesus monkey cDNA and subsequently identified in OWM and apes but not in humans. Rhesus CD209L2 mRNA was prominently expressed in the liver and axillary lymph nodes, although preliminary data suggest that levels of expression may vary among individuals. Despite a high level of sequence similarity to both human and rhesus CD209, rhesus CD209L2 was substantially less effective at binding ICAM-3 and poorly transmitted HIV type 1 and SIV to target cells relative to CD209. Our data suggest that the CD209 gene family has undergone recent evolutionary processes involving duplications and deletions, the latter of which may be tolerated because of potentially redundant functional activities of the molecules encoded by these genes.
机译:在人类中鉴定出的两个CD209家族基因CD209(DC-SIGN)和CD209L(DC-SIGNR / L-SIGN)编码C型凝集素,它们充当ICAM-2和ICAM-3的粘附受体,并参与ICAM-2和ICAM-3的传递。人和猿猴免疫缺陷病毒(分别为HIV和SIV)感染体外靶细胞。在这里,我们表征了非人类灵长类动物中的CD209基因家族,并显示了该家族中跨灵长类物种的最近进化变化。测试的所有灵长类物种,特别是旧大陆猴子(OWM)和猿类,都具有人类CD209直系同源物。相反,OWM中缺少CD209L,但猿类中存在。从恒河猴cDNA克隆了我们命名为CD209L2的第三个家族成员,随后在OWM和猿类中进行了鉴定,但未在人类中进行鉴定。恒河猴CD209L2 mRNA在肝脏和腋窝淋巴结中显着表达,尽管初步数据表明表达水平可能因人而异。尽管与人和恒河猴CD209都有很高的序列相似性,但恒河猴CD209L2相对于CD209结合ICAM-3的效率明显较低,并且1型和SIV型HIV与靶细胞的传播较差。我们的数据表明,CD209基因家族已经经历了最近的进化过程,涉及重复和缺失,由于这些基因编码的分子可能具有多余的功能活性,因此可以容忍后者。

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