Human rElafin Inhibits HIV-1 Replication in Its Natural Target Cells

Abstract

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.

Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers

“…SERPINB1 belongs to the serine protease inhibitor family of antiproteases, and inhibits both elastase-like and chymotrypsin-like proteases, including Cathepsin G. It has been implicated in providing defense against microorganisms at mucosal surfaces by protecting against protease-mediated inflammatory damage of the epithelium induced during bacterial infections, and promoting wound healing [ 50 ]. Other serine protease inhibitors such as Serpin A1, Secreted leukocyte protease inhibitor and Elafin have been associated with anti-HIV functionality in vitro [ 51 – 54 ]. Therefore, SERPINB1 may represent a novel target for further study of its potential to neutralize HIV, thus preventing infection.…”

Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis

“…Women demonstrating resistance to HIV-1 infection have been shown to have a higher expression of Elafin with only the 6 kDa WAP motif in the reproductive organs [ 56 ]. Recombinant Elafin and Trappin-2 inhibit HIV-1 replication in T cells [ 57 , 58 ]. The Trappin family was formed through gene duplication, especially in porcine relatives, and underwent accelerated evolution [ 59 , 60 ].…”

Factores solubles con actividad antiviral: en búsqueda de nuevos blancos terapéuticos para la infección por el VIH-1

“…Se han encontrado concentraciones altas de ELAFIN en el tracto genital de las mujeres que han estado expuestas al VIH y no se han infectado, en comparación con las no expuestas o VIH positivas, lo que ha llevado a sugerir que ELAFIN es un factor innato, relacionado con la protección natural frente a la infección adquirida durante las relaciones vaginales (62,63).…”