Inhibition of cellular factor TM6SF2 suppresses secretion pathways of Hepatitis B, Hepatitis C and Hepatitis D viruses.
Thomas TuHarout AjoyanRifqiyah Nur UmamiVaishnavi VeeraraghavanDelgerbat BoldbaatarMustafa Ahmed M NajimAnis KhanAli BayoumiVikki HoMohammed EslamThomas BergHenry L Y ChanJacob GeorgeMark W DouglasPublished in: The Journal of infectious diseases (2024)
Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all 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.
Keyphrases
- hepatitis b virus
- hepatitis c virus
- endoplasmic reticulum
- human immunodeficiency virus
- liver failure
- sars cov
- computed tomography
- protein protein
- small molecule
- human health
- magnetic resonance imaging
- magnetic resonance
- amino acid
- transcription factor
- image quality
- bone marrow
- dual energy
- drug induced
- hiv infected
- cell therapy