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Monitoring reversion of hepatitis C virus-induced cellular alterations by direct-acting antivirals using cryo soft X-ray tomography and infrared microscopy

ABSTRACT: The study of cells replicating hepatitis C and treated with antiviral compounds by soft X-ray cryo tomography (cryo-SXT) and synchrotron-based infrared microscopy allows correlation of the viral structures resolved by the former with their chemical composition revealed by the latter. The results show the potential of cryo-SXT as a platform to determine the effectiveness of antiviral compounds in infected cells, guiding drug development at a preclinical level. Hepatitis C virus (HCV) is an enveloped RNA virus. One of the hallmarks of HCV infection is a rearrangement of the host cell membranes, known as the ‘membranous web’. Full-field cryo soft X-ray tomography (cryo-SXT) in the water-window energy range (284–543 eV) was performed on the MISTRAL beamline to investigate, in whole unstained cells, the morphology of the membranous rearrangements induced in HCV replicon-harbouring cells in conditions close to the living physiological state. All morphological alterations could be reverted by a combination of sofosbuvir/daclatasvir, which are clinically approved antivirals (direct-acting antivirals; DAAs) for HCV infection. Correlatively combining cryo-SXT and 2D synchrotron-based infrared microscopy provides critical information on the chemical nature of specific infection-related structures, which allows specific patterns of the infection process or the DAA-mediated healing process to be distinguished.

SUBMITTER: Perez-Berna A

PROVIDER: S-EPMC8561738 | biostudies-literature |

REPOSITORIES: biostudies-literature

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