Abstract
Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SP-D against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection.
Highlights
Acute HIV infection is marked by a pro-inflammatory ‘‘cytokine storm’’ that promotes viral replication and mediate immunopathology [1]
We report that the anti-HIV-1 properties of recombinant fragment of human Seminal plasma (SP)-D (rhSP-D) remain unaltered in the presence of cervicovaginal lavage and seminal plasma, raising the possibility that the recombinant protein may have a prophylactic value
Here, we show the anti-HIV-1 activity of a recombinant fragment of human SP-D containing trimeric carbohydrate recognition domain (CRD) and its ability to contain the viral replication in Jurkat T cells, U937 monocytes and activated Peripheral Blood Mononuclear Cells (PBMCs) in vitro
Summary
Acute HIV infection is marked by a pro-inflammatory ‘‘cytokine storm’’ that promotes viral replication and mediate immunopathology [1]. This leads to a non-specific activation and proliferation of naıve CD4+ T cells providing the ideal microenvironment for viral replication. Infected CD4+ T cells are known to induce levels of IL-2, IL-6, and TNF-a and synergistically induce HIV-1 replication [3]. These series of events lead to successful viral entry and dissemination. Recent anti-HIV-1 vaccine design and prevention strategies are focused on regulating such initial, generalized immune activation that can curb viral replication [4]
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