Pro-fibrogenic role of alarmin high mobility group box 1 in HIV-hepatitis B virus coinfection.


Journal

AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219

Informations de publication

Date de publication:
01 03 2023
Historique:
pubmed: 18 11 2022
medline: 27 1 2023
entrez: 17 11 2022
Statut: ppublish

Résumé

Liver disease is accelerated in people with HIV (PWH) with hepatitis B virus (HBV) coinfection. We hypothesized that liver fibrosis in HIV-HBV is triggered by increased hepatocyte apoptosis, microbial translocation and/or HIV/HBV viral products. Sera from PWH with HBV coinfection versus from those with HBV only or putative mediators were used to examine the pathogenesis of liver disease in HIV-HBV. We applied sera from PWH and HBV coinfection versus HBV alone, or putative mediators (including HMGB1), to primary human hepatic stellate cells (hHSC) and examined pro-fibrogenic changes at the single cell level using flow cytometry. High mobility group box 1 (HMGB1) levels in the applied sera were assessed according to donor fibrosis stage. Quantitative flow cytometric assessment of pro-fibrogenic and inflammatory changes at the single cell level revealed an enhanced capacity for sera from PWH with HBV coinfection to activate hHSC. This effect was recapitulated by lipopolysaccharide, HIV-gp120, hepatocyte conditioned-media and the alarmin HMGB1. Induction of hepatocyte cell death increased their pro-fibrogenic potential, an effect blocked by HMGB1 antagonist glycyrrhizic acid. Consistent with a role for this alarmin, HMGB1 levels were elevated in sera from PWH and hepatitis B coinfection compared to HBV alone and higher in those with HIV-HBV with liver fibrosis compared to those without. Sera from PWH and HBV coinfection have an enhanced capacity to activate primary hHSC. We identified an increase in circulating HMGB1 which, in addition to HIV-gp120 and translocated microbial products, drove pro-fibrogenic changes in hHSC, as mechanisms contributing to accelerated liver disease in HIV-HBV.

Identifiants

pubmed: 36384811
doi: 10.1097/QAD.0000000000003435
pii: 00002030-202303010-00004
doi:

Substances chimiques

Alarmins 0
HMGB1 Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

401-411

Subventions

Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901374
Pays : United Kingdom

Informations de copyright

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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Auteurs

Kasha P Singh (KP)

Division of Infection and Immunity, University College London, London, UK.
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity.
Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity.
Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia.

Laura J Pallett (LJ)

Division of Infection and Immunity, University College London, London, UK.

Harsimran Singh (H)

Division of Infection and Immunity, University College London, London, UK.
Institute for Liver and Digestive Health, University College London, London, UK.

Antony Chen (A)

Division of Infection and Immunity, University College London, London, UK.

Itziar Otano (I)

Division of Infection and Immunity, University College London, London, UK.

Marion Duriez (M)

Division of Infection and Immunity, University College London, London, UK.

Krista Rombouts (K)

Institute for Liver and Digestive Health, University College London, London, UK.

Massimo Pinzani (M)

Institute for Liver and Digestive Health, University College London, London, UK.

Megan Crane (M)

Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity.

Giuseppe Fusai (G)

Institute for Liver and Digestive Health, University College London, London, UK.

Anchalee Avihingsanon (A)

HIV-NAT, Thai Red Cross AIDS Research Center (TRCARC), Bangkok, Thailand.

Sharon R Lewin (SR)

Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity.
Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity.
Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia.

Mala K Maini (MK)

Division of Infection and Immunity, University College London, London, UK.

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