Abstract

BackgroundChronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS) in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV)-infected rhesus macaques of Chinese origin.MethodsThe animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL) test.ResultsThe animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs.ConclusionsThese data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.

Highlights

  • HIV infection is characterized by systemic immune activation, which is a major cause of progressive HIV disease

  • We investigated the impact of LPS administration on systemic immune activation and viral replication in simian immunodeficiency virus (SIV)-infected rhesus macaques of Chinese origin

  • The kinetics of plasma viral load were similar in all SIV-infected animals and the peak levels of the viral loads occurred at week 2 postinfection (Fig. 1A)

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Summary

Introduction

HIV infection is characterized by systemic immune activation, which is a major cause of progressive HIV disease. Microbial translocation has been suggested as a possible mechanism of systemic immune activation in individuals with chronic HIV infection. LPS in the circulation has been implicated as a key microbial product that contributes to HIV infection-related systemic immune activation [1]. LPS levels were significantly higher in individuals with chronic HIV infection than the control group [1]. Elevated LPS levels in blood are likely responsible for systemic immune activation in chronic HIV infection. Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS) in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV)-infected rhesus macaques of Chinese origin

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