Jasinghe Viraj J, Peyrotte Erika Arnau, Meyers Adrienne F A, Gajanayaka Niranjala, Ball Terry B, Sandstrom Paul, Lavigne Carole
National HIV and Retrovirology Laboratories, National Microbiology Laboratory , Public Health Agency of Canada, Ottawa, Canada .
Biores Open Access. 2013 Apr;2(2):128-37. doi: 10.1089/biores.2012.0275.
Trappin-2/elafin is a novel innate immune factor that belongs to the serine protease inhibitor family and has known antibacterial, antifungal, and antiviral properties. In this study, we further investigated the anti-HIV activity of elafin using different cellular models and both X4- and R5-HIV-1 laboratory strains. We compared the antiviral activity of human recombinant elafin (rElafin) with three well-known antiretroviral drugs, AZT, tenofovir, and enfuvirtide. We have found that when the virus is pre-incubated with rElafin prior to the infection of the cells, HIV-1 replication is significantly inhibited. In target T cells and human peripheral blood mononuclear cells, maximal inhibition was achieved using submicromolar concentrations, and rElafin was found to be as potent as enfuvirtide, showing its potential for therapeutic application. We also show data on the mechanism of the antiviral activity of rElafin. We have demonstrated that rElafin neither binds to CD4, CXCR4, or CCR5 host cell receptors, nor to the viral glycoproteins gp120 and gp41. Furthermore, in our cell-to-cell fusion assays, in contrast to enfuvirtide, rElafin failed to block cell fusion. Altogether our results indicate that rElafin interferes with HIV replication at the early steps of its cycle but with a different mechanism of action than enfuvirtide. This study provides the first experimental evidence that elafin inhibits HIV replication in its natural target cells; therefore, elafin might have potential for its development as a new anti-HIV drug or microbicide.
Trappin-2/elafin是一种新型的固有免疫因子，属于丝氨酸蛋白酶抑制剂家族，具有已知的抗菌、抗真菌和抗病毒特性。在本研究中，我们使用不同的细胞模型以及X4和R5型HIV-1实验室毒株，进一步研究了elafin的抗HIV活性。我们将重组人elafin（rElafin）的抗病毒活性与三种知名抗逆转录病毒药物齐多夫定（AZT）、替诺福韦和恩夫韦肽进行了比较。我们发现，当病毒在感染细胞之前与rElafin预孵育时，HIV-1复制受到显著抑制。在靶T细胞和人外周血单个核细胞中，使用亚微摩尔浓度可实现最大抑制，并且发现rElafin与恩夫韦肽一样有效，显示出其治疗应用潜力。我们还展示了关于rElafin抗病毒活性机制的数据。我们已经证明，rElafin既不与CD4、CXCR4或CCR5宿主细胞受体结合，也不与病毒糖蛋白gp120和gp41结合。此外，在我们的细胞间融合试验中，与恩夫韦肽不同，rElafin未能阻断细胞融合。总之，我们的结果表明，rElafin在HIV周期的早期阶段干扰其复制，但作用机制与恩夫韦肽不同。本研究提供了首个实验证据，证明elafin在其天然靶细胞中抑制HIV复制；因此，elafin可能有潜力开发成为一种新型抗HIV药物或杀微生物剂。
