Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
J Biol Chem. 2010 Mar 19;285(12):8646-55. doi: 10.1074/jbc.M109.034926. Epub 2010 Jan 15.
BanLec is a jacalin-related lectin isolated from the fruit of bananas, Musa acuminata. This lectin binds to high mannose carbohydrate structures, including those found on viruses containing glycosylated envelope proteins such as human immunodeficiency virus type-1 (HIV-1). Therefore, we hypothesized that BanLec might inhibit HIV-1 through binding of the glycosylated HIV-1 envelope protein, gp120. We determined that BanLec inhibits primary and laboratory-adapted HIV-1 isolates of different tropisms and subtypes. BanLec possesses potent anti-HIV activity, with IC(50) values in the low nanomolar to picomolar range. The mechanism for BanLec-mediated antiviral activity was investigated by determining if this lectin can directly bind the HIV-1 envelope protein and block entry of the virus into the cell. An enzyme-linked immunosorbent assay confirmed direct binding of BanLec to gp120 and indicated that BanLec can recognize the high mannose structures that are recognized by the monoclonal antibody 2G12. Furthermore, BanLec is able to block HIV-1 cellular entry as indicated by temperature-sensitive viral entry studies and by the decreased levels of the strong-stop product of early reverse transcription seen in the presence of BanLec. Thus, our data indicate that BanLec inhibits HIV-1 infection by binding to the glycosylated viral envelope and blocking cellular entry. The relative anti-HIV activity of BanLec compared favorably to other anti-HIV lectins, such as snowdrop lectin and Griffithsin, and to T-20 and maraviroc, two anti-HIV drugs currently in clinical use. Based on these results, BanLec is a potential component for an anti-viral microbicide that could be used to prevent the sexual transmission of HIV-1.
BanLec 是从香蕉果实(Musa acuminata)中分离出的一种 Jacalin 相关凝集素。这种凝集素与高甘露糖碳水化合物结构结合,包括那些在含有糖基化包膜蛋白的病毒上发现的结构,例如人类免疫缺陷病毒 1 型(HIV-1)。因此,我们假设 BanLec 可能通过结合糖基化的 HIV-1 包膜蛋白 gp120 来抑制 HIV-1。我们确定 BanLec 可以抑制不同嗜性和亚型的原发性和实验室适应的 HIV-1 分离株。BanLec 具有强大的抗 HIV 活性,IC50 值在纳摩尔到皮摩尔范围内。通过确定这种凝集素是否可以直接结合 HIV-1 包膜蛋白并阻止病毒进入细胞,研究了 BanLec 介导的抗病毒活性的机制。酶联免疫吸附试验证实了 BanLec 与 gp120 的直接结合,并表明 BanLec 可以识别被单克隆抗体 2G12 识别的高甘露糖结构。此外,BanLec 能够阻止 HIV-1 细胞进入,如热敏性病毒进入研究和 BanLec 存在时早期逆转录的强终止产物水平降低所表明的那样。因此,我们的数据表明,BanLec 通过与糖基化的病毒包膜结合并阻止细胞进入来抑制 HIV-1 感染。BanLec 的相对抗 HIV 活性优于其他抗 HIV 凝集素,例如雪花莲凝集素和 Griffithsin,以及两种抗 HIV 药物 T-20 和马拉维若,目前正在临床使用。基于这些结果,BanLec 是一种潜在的抗病毒杀微生物剂成分,可用于预防 HIV-1 的性传播。