Naturally Derived Anti-HIV Polysaccharide Peptide (PSP) Triggers a Toll-Like Receptor 4-Dependent Antiviral Immune Response.

Luis Cubano,Sheila López,Eddy Ríos-Olivares,Nawal M. Boukli,Mariela Rivera,Madeline Rodríguez-Valentín

doi:10.1155/2018/8741698

Luis Cubano, Sheila López + Show 4 more

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https://doi.org/10.1155/2018/8741698

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Abstract

Aim Intense interest remains in the identification of compounds to reduce human immunodeficiency virus type 1 (HIV-1) replication. Coriolus versicolor's polysaccharide peptide (PSP) has been demonstrated to possess immunomodulatory properties with the ability to activate an innate immune response through Toll-like receptor 4 (TLR4) showing insignificant toxicity. This study sought to determine the potential use of PSP as an anti-HIV agent and whether its antiviral immune response was TLR4 dependent. Materials and Methods HIV-1 p24 and anti-HIV chemokine release was assessed in HIV-positive (HIV+) THP1 cells and validated in HIV+ peripheral blood mononuclear cells (PBMCs), to determine PSP antiviral activity. The involvement of TLR4 activation in PSP anti-HIV activity was evaluated by inhibition. Results PSP showed a promising potential as an anti-HIV agent, by downregulating viral replication and promoting the upregulation of specific antiviral chemokines (RANTES, MIP-1α/β, and SDF-1α) known to block HIV-1 coreceptors in THP1 cells and human PBMCs. PSP produced a 61% viral inhibition after PSP treatment in HIV-1-infected THP1 cells. Additionally, PSP upregulated the expression of TLR4 and TLR4 inhibition led to countereffects in chemokine expression and HIV-1 replication. Conclusion Taken together, these findings put forward the first evidence that PSP exerts an anti-HIV activity mediated by TLR4 and key antiviral chemokines. Elucidating these new molecular mediators may reveal additional drug targets and open novel therapeutic avenues for HIV-1 infection.

Highlights

In the early 1980s, the human immunodeficiency virus type 1 (HIV-1) retrovirus was identified as the causative agent of acquired immunodeficiency syndrome (AIDS), one of the most devastating infectious diseases that have emerged in recent history [1, 2]
Further investigations are required to assess the role of polysaccharide peptide (PSP) in HIV infection. This current study reveals for the first time the promising potential of PSP in THP1 cells and human peripheral blood mononuclear cells (PBMCs), as an anti-HIV agent, by downregulating viral replication and promoting the upregulation of Toll-like receptor 4 (TLR4), leading to the production of antiHIV-1 chemokines (RANTES, MIP-1α/β, and SDF-1α) known to block HIV-1 coreceptors
These results suggest that a PSP concentration of 200 μg/ml during a 6-day period is the half maximal effective concentration to achieve a high significant difference in activation of NFκβ in THP1 cells without producing major cytotoxic effects

Summary

Introduction

In the early 1980s, the human immunodeficiency virus type 1 (HIV-1) retrovirus was identified as the causative agent of acquired immunodeficiency syndrome (AIDS), one of the most devastating infectious diseases that have emerged in recent history [1, 2]. Viruses have evolved a wide variety of strategies by which they maintain long-term infection of populations. HIV-1’s ability to establish reservoirs allows it to maintain a persistent infection, making it difficult to eradicate [3]. Antiretroviral therapies (ART) have been shown to extend the life of patients [4] by preservation of HIV-1-specific CD4+ cells and by lowering the level of HIV-1 viral replication, thereby reducing infectivity and preventing AIDS-related diseases [5]. New ART regimens show lower cytotoxicity, these medications are expensive for underprivileged communities [6, 7] and continue to produce side effects [8], leading to adherence and treatment failure [9, 10]. New nontoxic and inexpensive therapies are needed to reduce HIV-1 infectivity

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