Elevated plasma levels of lipopolysaccharide and high mobility group box-1 protein are associated with high viral load in HIV-1 infection: reduction by 2-year antiretroviral therapy

Trøseid, Marius; Nowak, Piotr; Nyström, Jessica; Lindkvist, Annica; Abdurahman, Samir; Sönnerborg, Anders

doi:10.1097/qad.0b013e32833b254d

Cited by 66 publications

(63 citation statements)

References 19 publications

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“…16,17,30,31 It was observed that, when compared with negative controls, the plasma of HIV-1-infected patients contains higher HMGB1 concentrations, which can be correlated to the viral load. 19,32 In the case of West Nile Virus (WNV), depending on the viral dose, the infected cells undergo necrosis, and the concomitant release of HMGB1 contributes to the disease pathology. 33 In addition, the HMGB1 levels were significantly higher in patients with severe pneumonia caused by influenza virus.…”

Section: Discussionmentioning

confidence: 99%

Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection

Allonso

Belgrano

Calzada

et al. 2012

Journal of Clinical Virology

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Section: Discussionmentioning

confidence: 99%

Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection

Allonso

Belgrano

Calzada

et al. 2012

Journal of Clinical Virology

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“…Moreover, gut epithelial barrier dysfunction [8] as well as high levels of sCD14 [9] predicts mortality in HIV infection. Immune activation and microbial translocation are reduced, but often not normalized despite prolonged effective ART with achievement of viral suppression [4,[10][11][12]. Importantly, increased cardiovascular risk has been linked to lack of CD4 cell count restoration despite effective ART [13,14], which in turn is associated with low nadir CD4 cell counts [15], persistent microbial translocation [12] and immune activation [10].…”

Section: Introductionmentioning

confidence: 99%

“…Plasma samples were collected with standard venipuncture as per clinical practice, and fasting state had been recommended but was not recorded. The samples were stored at -20°C until analysis.LPS was analysed using the Limulus Amebocyte Lysate colorimetric assay (Lonza, Walkersville, MD) according to the manufacturer's instructions, with the following modifications: samples were diluted 10-fold to avoid interference with background colour, and preheated to 68°C for 12 min prior to analyses to dissolve immune complexes, as previously described [11]. sCD14 was analysed using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions (R&D, Minneapolis, MN).…”

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confidence: 99%

Markers of microbial translocation predict hypertension in HIV‐infected individuals

et al. 2013

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ObjectivesThe aim of the study was to test the hypothesis that microbial translocation, quantified by levels of lipopolysaccharide (LPS) and subsequent monocyte activation [soluble (sCD14)], is associated with hypertension in HIV-infected individuals. MethodsIn this exploratory substudy, 42 patients were recruited from a larger, longitudinal HIV-infected cohort study on blood pressure. LPS and sCD14 levels were measured retrospectively at the time of nadir CD4 cell count, selecting untreated HIV-infected patients with both advanced immunodeficiency and preserved immunocompetence at the time of nadir. Patients with later sustained hypertension (n = 16) or normotension (n = 26) throughout the study were identified. LPS was analysed using the Limulus Amebocyte Lysate colorimetric assay (Lonza, Walkersville, MD) and sCD14 using an enzyme-linked immunosorbent assay (ELISA). Nonparametric statistical tests were applied. ResultsIn the HIV-infected patients [median (interquartile range) age 42 (32-46) years; 79% male and 81% Caucasian], LPS and sCD14 levels were both negatively correlated with nadir CD4 cell count. Plasma levels of LPS (P < 0.001) and sCD14 (P = 0.024) were elevated in patients with later hypertension compared with patients with normotension. There was a stepwise increase in the number of patients with hypertension across tertiles of LPS (P = 0.001) and sCD14 (P = 0.007). Both LPS and sCD14 were independent predictors of elevated blood pressure after adjustment for age and gender. For each 10-unit increase in LPS (range 66-272 pg/ml), the increment in mean blood pressure in the first period of blood pressure recording was 0.86 (95% confidence interval 0.31-1.41) mmHg (P = 0.003). ConclusionsAs LPS and sCD14 were both independently associated with elevated blood pressure, microbial translocation may be linked to the development of hypertension.Keywords: HIV infection, hypertension, lipopolysaccharide, nadir CD4 cell count, soluble CD14. Accepted 5 December 2012 IntroductionNon-AIDS-related morbidities such as hypertension, cardiovascular disease (CVD), malignancy, and renal, liver and bone diseases have emerged as increasing clinical problems in HIV-infected patients [1]. In fact, non-AIDS-related mortality today exceeds AIDS-related mortality in populations with access to antiretroviral therapy (ART) [2]. A premature ageing process has been suggested to occur in HIV-infected individuals for which several contributing factors have been proposed, including viral replication, drug toxicity, lifestyle factors, and persistent immune Primary HIV infection is characterized by massive T-cell depletion in the gastrointestinal mucosa with subsequent enhanced translocation of bacterial products such as lipopolysaccharide (LPS) and flagellin from the intestinal lumen into the systemic circulation [3,4]. LPS is a potent inducer of immune response and inflammation through the innate immune system. Soluble CD14 (sCD14) is a marker of monocyte activation and is shed from monocytes upon LPS stimulation [5]. Microbial tr...

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“…28 (4) HMGB1 forms highly inflammatory complexes with LPS, and signals through the TLR4; 95 (5) an association of elevated circulating levels of LPS and high viral load was reported in HIV-infected patients. 90 Thus, HMGB1-LPS complexes may be important in perpetuating inflammatory amplification loops in HIV disease. Thus, HMGB1 by itself, or combined to LPS or other TLR ligand or cytokines, may induce a self-perpetuating cycle by contributing to immune activation that creates new T-cell targets for viral infection and subsequent increased rate of cell death and release of HMGB1, but also by stimulating HIV replication and viral persistence in DCs.…”

Section: Hmgb1 Immune Activation and Hiv-1 Disease Progressionmentioning

confidence: 99%

“…89 Plasma levels of HMGB1 are elevated during the course of HIV-1 infection 17 and positively associated with high viral load. 90 HMGB1 can be passively released by virus-infected cells including primary CD4 T cells infected with HIV-1, and this was associated with both necrotic and apoptotic cell death.…”

Section: Hmgb1 Immune Activation and Hiv-1 Disease Progressionmentioning

confidence: 99%

HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells

Gougeon

Saïdi

2011

Cell Death Differ

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Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense. It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells. The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK-DC synapse. HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells. This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis.

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Elevated plasma levels of lipopolysaccharide and high mobility group box-1 protein are associated with high viral load in HIV-1 infection: reduction by 2-year antiretroviral therapy

Cited by 66 publications

References 19 publications

Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection

Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection

Markers of microbial translocation predict hypertension in HIV‐infected individuals

HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells

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