RT Journal Article
T1 Phosphodiesterase-induced cAMP degradation restricts hepatitis B virus infection.
A1 Evripioti, Antonia Alexandra
A1 Ortega-Prieto, Ana María
A1 Skelton, Jessica Katy
A1 Bazot, Quentin
A1 Dorner, Marcus
K1 Virología - Investigación
K1 Virus de la hepatitis
K1 Hepatitis - Tratamiento
AB Hepatitis B virus (HBV) entry into hepatocytes is mediated via a high-affinity interaction between the preS1 glycoprotein and sodium/bile acid cotransporting polypeptide (NTCP). To date, in vitro model systems rely on high multiplicities of infection to achieve infection of cell lines overexpressing human NTCP. This study investigates a novel regulatory pathway for NTCP trafficking to the cell surface, induced by DMSO-mediated cellular differentiation. DMSO rapidly induces high cell surface expression of NTCP and results in increased susceptibility of cells to HBV infection. Additionally, DMSO treatment induces actin, as well as Tubulin reshaping within the cells. We show that direct disruption of the actin and Tubulin network directly enhances NTCP expression and the subsequent susceptibility of cells to HBV infection. DMSO induces these changes via alterations in the levels of cyclic (c)AMP, which participates in the observed actin rearrangements. Blocking of phosphodiesterases (PDEs), which degrade accumulated cAMP, had the same effect as DMSO differentiation and demonstrates that DMSO prevents phosphodiesterase-mediated cAMP degradation. This identifies adenylate cyclase as a novel target for blocking the entry of HBV via targeting the cell surface accumulation of NTCP. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
PB The Royal Society
YR 2019
FD 2019-04-08
LK https://hdl.handle.net/10630/35420
UL https://hdl.handle.net/10630/35420
LA eng
NO Evripioti Antonia Alexandra, Ortega-Prieto Ana Maria, Skelton Jessica Katy, Bazot Quentin and Dorner Marcus 2019Phosphodiesterase-induced cAMP degradation restricts hepatitis B virus infectionPhil. Trans. R. Soc. B37420180292 http://doi.org/10.1098/rstb.2018.0292
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026