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Inhibition of cellular factor TM6SF2 suppresses secretion pathways of Hepatitis B, Hepatitis C and Hepatitis D viruses.
Tu, Thomas; Ajoyan, Harout; Nur Umami, Rifqiyah; Veeraraghavan, Vaishnavi; Boldbaatar, Delgerbat; Najim, Mustafa Ahmed M; Khan, Anis; Bayoumi, Ali; Ho, Vikki; Eslam, Mohammed; Berg, Thomas; Chan, Henry L Y; George, Jacob; Douglas, Mark W.
Afiliação
  • Tu T; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Ajoyan H; Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Nur Umami R; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Veeraraghavan V; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Boldbaatar D; Research Center for Genetic Engineering, National Research and Innovation Agency (BRIN), Bogor, Indonesia.
  • Najim MAM; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Khan A; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Bayoumi A; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Ho V; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Eslam M; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Berg T; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Chan HLY; Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • George J; Division of Hepatology, Department of Medicine II, Leipzig University Medical Centre, Germany.
  • Douglas MW; The Chinese University of Hong Kong, Shatin, NT , Hong Kong SAR, The People's Republic of China.
J Infect Dis ; 2024 Feb 26.
Article em En | MEDLINE | ID: mdl-38408366
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Infect Dis / J. infect. dis / Journal of infectious diseases Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Infect Dis / J. infect. dis / Journal of infectious diseases Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Austrália