Microvirin, a Novel α(1,2)-Mannose-specific Lectin Isolated from Microcystis aeruginosa, Has Anti-HIV-1 Activity Comparable with That of Cyanovirin-N but a Much Higher Safety Profile
Microvirin, a Novel α(1,2)-Mannose-specific Lectin Isolated from Microcystis aeruginosa, Has Anti-HIV-1 Activity Comparable with That of Cyanovirin-N but a Much Higher Safety Profile
复制标题
DOI：
10.1074/jbc.m110.128546
复制
发表时间：
2010-08-06
影响因子：
4.8
通讯作者：
Schols, Dominique
中科院分区：
文献类型：
--
作者：
Huskens, Dana;Ferir, Geoffrey;Schols, Dominique
微病毒素(Microvirin，MVN)是最近从铜绿微囊藻PCC7806中分离得到的凝集素，与从发菜中分离到的强大的抗人类免疫缺陷病毒(HIV)蛋白氰病毒素-N(CV-N)有33%的同源性，并且两者都与相似的碳水化合物结构结合。MVN能够抑制多种HIV-1实验室适应毒株和不同嗜性和亚型的临床分离株在外周血单核细胞中的感染。MVN还抑制持续感染HIV-1的T细胞和未感染的CD4(+)T细胞之间的合胞体形成，并抑制DC-SIGN介导的HIV-1结合和向CD4(+)T细胞的传播。长期传代暴露在剂量递增浓度的MVN下的HIV-1导致了一种突变病毒的选择，该病毒的包膜gp120中有四个缺失的高甘露糖型多糖。MVN抗性病毒仍然对其他各种碳水化合物结合凝集素(如CV-N、HHA、GNA和UDA)高度敏感，但对碳水化合物特异性2G12单抗不再敏感。重要的是，MVN的细胞毒性比CV-N低50多倍。同样与CV-N形成鲜明对比的是，MVN没有增加CD4(+)T淋巴细胞中CD25、CD69和HLA-DR的激活标志水平，随后MVN也没有促进经处理的外周血单个核细胞中的病毒复制。因此，基于其广泛而有效的抗病毒活性以及几乎没有任何刺激特性和细胞毒性，MVN可能有资格作为一种有用的凝集素用于潜在的杀菌用途。
Microvirin (MVN), a recently isolated lectin from the cyanobacterium Microcystis aeruginosa PCC7806, shares 33% identity with the potent anti-human immunodeficiency virus (HIV) protein cyanovirin-N (CV-N) isolated from Nostoc ellipsosporum, and both lectins bind to similar carbohydrate structures. MVN is able to inhibit infection by a wide variety of HIV-1 laboratory-adapted strains and clinical isolates of different tropisms and subtypes in peripheral blood mononuclear cells. MVN also inhibits syncytium formation between persistently HIV-1-infected T cells and uninfected CD4(+) T cells and inhibits DC-SIGN-mediated HIV-1 binding and transmission to CD4(+) T cells. Long term passaging of HIV-1 exposed to dose-escalating concentrations of MVN resulted in the selection of a mutant virus with four deleted high mannose-type glycans in the envelope gp120. The MVN-resistant virus was still highly sensitive to various other carbohydrate binding lectins (e.g. CV-N, HHA, GNA, and UDA) but not anymore to the carbohydrate-specific 2G12 monoclonal antibody. Importantly, MVN is more than 50-fold less cytotoxic than CV-N. Also in sharp contrast to CV-N, MVN did not increase the level of the activation markers CD25, CD69, and HLA-DR in CD4(+) T lymphocytes, and subsequently, MVN did not enhance viral replication in pretreated peripheral blood mononuclear cells. Therefore, MVN may qualify as a useful lectin for potential microbicidal use based on its broad and potent antiviral activity and virtual lack of any stimulatory properties and cellular toxicity.