Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses-Reference-Cited by-同舟云学术

Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses

Published:2024-02-26 Issue: Volume: Page:
ISSN:0022-1899
Container-title:The Journal of Infectious Diseases
language:en
Short-container-title:

Author:

Tu Thomas¹²^ORCID,Ajoyan Harout¹,Nur Umami Rifqiyah¹³,Veeraraghavan Vaishnavi¹,Boldbaatar Delgerbat¹,Najim Mustafa Ahmed M¹,Khan Anis¹,Bayoumi Ali¹,Ho Vikki¹,Eslam Mohammed¹,Berg Thomas⁴,Chan Henry L Y⁵⁶,George Jacob¹,Douglas Mark W¹²^ORCID

Affiliation:

1. Storr Liver Centre, The Westmead Institute for Medical Research

2. Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital , Westmead, New South Wales , Australia

3. Research Center for Genetic Engineering, National Research and Innovation Agency , Bogor , Indonesia

4. Division of Hepatology, Department of Medicine II, Leipzig University Medical Centre , Germany

5. Faculty of Medicine, The Chinese University of Hong Kong

6. Department of Internal Medicine, Union Hospital , Hong Kong Special Administrative Region , People's Republic of China

Abstract

Abstract Chronic viral hepatitis is caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). Despite different replication strategies, all of these viruses rely on secretion through the host endoplasmic reticulum–Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions, and HBV subviral particles. Moreover, in a cohort of people with hepatitis B, a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV, and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.

Funder

Paul and Valeria Ainsworth Precision Medicine Fellowship

Australian National Health and Medical Research Council

Australian Centre for HIV and Hepatitis Virology Research

Australian Department of Foreign Affairs and Trade Australia Award Scholarship

University of Sydney DVC Research

Postdoctoral Research Fellowship Scheme

University of Sydney Postgraduate Award

Faculty of Medicine and Health Executive Dean Stipend Scholarship

Kingdom of Saudi Arabia

Ministry of Health PhD Overseas Scholarship

Robert W. Storr Bequest to the Sydney Medical Foundation