Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

Tugizov, Sharof M.

doi:10.1080/21688370.2016.1159276

Cited by 42 publications

(52 citation statements)

References 145 publications

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“…That intestinal HIV-1 antibodies recognized these proteins, expressed to different degrees in circulating mononuclear cells or the gut, could be fortuitous and because of sequence and/or structural homology. The cross-reactivity to MAPK14 is intriguing because the MAPK14/p38 signaling pathway is a master regulator of various cellular activities, with some implicated in HIV-1 replication and pathogenesis, such as T cell and mucosal epithelial cell apoptosis ( Furler and Uittenbogaart, 2010 , Nardacci et al., 2015 , Tugizov, 2016 ). One pathological immune consequence of CD4 + T cell apoptosis is the cross-presentation of self-antigens capable of inducing autoreactive CD8 + T cell responses ( Rawson et al., 2007 ).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

et al. 2019

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Summary Mucosal immune responses to HIV-1 involve the recognition of the viral envelope glycoprotein (gp)160 by tissue-resident B cells and subsequent secretion of antibodies. To characterize the B cells “sensing” HIV-1 in the gut of infected individuals, we probed monoclonal antibodies produced from single intestinal B cells binding to recombinant gp140 trimers. A large fraction of mucosal B cell antibodies were polyreactive and showed only low affinity to HIV-1 envelope glycoproteins, particularly the gp41 moiety. A few high-affinity gp140 antibodies were isolated but lacked neutralizing, potent ADCC, and transcytosis-blocking capacities. Instead, they displayed cross-reactivity with defined self-antigens. Specifically, intestinal HIV-1 gp41 antibodies targeting the heptad repeat 2 region (HR2) cluster II cross-reacted with the p38α mitogen-activated protein kinase 14 (MAPK14). Hence, physiologic polyreactivity of intestinal B cells and molecular mimicry-based self-reactivity of HIV-1 antibodies are two independent phenomena, possibly diverting and/or impairing mucosal humoral immunity to HIV-1.

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Section: Discussionmentioning

confidence: 99%

HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

et al. 2019

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“…The lower incidence rate of HCV infection in HIV-negative MSM may partly be explained by the fact that HIV infection increases HCV susceptibility and transmission [ 14 ]. Indeed, HIV-associated disruption of mucosal epithelial junctions might facilitate the penetration and dissemination of HCV [ 15 , 16 ]. Likewise, MSM with HIV infection have higher seminal HCV loads than HIV-negative MSM which is known to promote HCV transmission [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C virus spread from HIV-positive to HIV-negative men who have sex with men

et al. 2018

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The aim of this study was to evaluate the potential transmission of HCV strains between HIV-positive men who have sex with men (MSM) and HIV-negative MSM. Since 2000, an ongoing epidemic of HCV infections is observed among HIV-positive MSM in high-income countries. However, HCV infections in HIV-negative MSM are investigated to a lesser extent due to the lack of follow-up in this population and only limited information is available on the risk of HCV transmission between HIV-positive MSM and HIV-negative MSM. We enrolled 49 MSM of which 43 were HIV-positive and 6 HIV-negative, including 4 being enrolled or waiting for enrolment in a preexposure prophylaxis (PrEP) program. All patients were diagnosed with acute HCV infection at the Infectious Disease Unit at the Hospices Civils de Lyon from 2014 to 2016. Risk factors for HCV infection were similar in both groups and included IV or nasal drug use, and rough sex practices. Typing and phylogenetic cluster analysis of HCV variants were performed by NS5B sequencing. Several clusters of infections were identified (genotype 1a: 3 clusters and 1 pair; genotype 4d: 1 cluster and 2 pairs), suggesting that several transmission events occurred within the study population. Every HCV strain identified in HIV-negative MSM was included in a cluster with HIV-positive MSM. Chronological analysis of contagiousness suggested the transmission of HCV from HIV-positive to HIV-negative patients. We conclude that recommendations for HCV surveillance should not be confined to HIV-positive MSM but should be extended to HIV-negative MSM with similar risk factors.

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“…Given that IEC represent an important source of IL-18 and HIV infection leads to a loss in gut barrier function and enhanced microbial translocation [ 3 , 23 , 24 ], we sought to investigate whether the virus has any effect on the expression and activation of this cytokine from these cell types. The issue gains more significance in view of the fact that gastro-intestinal tract (GIT)-associated lymphoid tissue is the primary site where HIV replicates and causes death of CD4+ T cells [ 25 , 26 ]. The localized viral replication compromises intestinal barrier function, which is normally maintained primarily by the Tight Junction (TJ) proteins comprising claudins, and occludin, etc; reviewed in [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation

et al. 2018

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Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple context dependent functions. We and others have shown that HIV infection is accompanied by increased circulating levels of IL-18 along with decreased levels of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is also accompanied by intestinal inflammation and decreased intestinal integrity as measured by intestinal permeability, regeneration and repair. However, little is known concerning the relation between high level of IL-18 associated with the viral infection and intestinal permeability. Here we demonstrate that HIV treatment increases production of IL-18 and decreases that of IL-18BP production in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the IEC by activating caspase-1 and caspase-3. It induces epithelial barrier hyperpermeability by decreasing and disrupting both tight and adherens junction proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was also observed in the IEC that were exposed to the cytokine. Moreover IL-18 decreases transepithelial electrical resistance (TEER) in Caco-2 and increases permeability in HT29 monolayers. The cells’ treatment with IL-18 causes an increase in the expression of phosphorylated myosin II regulatory light-chain (p-MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in p-MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the levels of the cytokine correlate with those of LPS in the circulation in three different categories of HIV infected patients (HAART-naïve and HAART-treated HIV-infected individuals, and Elite controls) as well as in healthy controls. Collectively, these results suggest that the HIV-induced IL-18 plays a role in increased intestinal permeability and microbial translocation observed in HIV-infected individuals.

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Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

Cited by 42 publications

References 145 publications

HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

Hepatitis C virus spread from HIV-positive to HIV-negative men who have sex with men

HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation

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