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Differences across cyclophilin A orthologs contribute to the host range restriction of hepatitis C virus.

Author(s): Gaska, Jenna M; Balev, Metodi; Ding, Qiang; Heller, Brigitte; Ploss, Alexander

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Abstract: The restricted host tropism of hepatitis C virus (HCV) remains incompletely understood, especially post-entry, and has hindered developing an immunocompetent, small animal model. HCV replication in non-permissive species may be limited by incompatibilities between the viral replication machinery and orthologs of essential host factors, like cyclophilin A (CypA). We thus compared the ability of CypA from mouse, tree shrew, and seven non-human primate species to support HCV replication, finding that murine CypA only partially rescued viral replication in Huh7.5-shRNA CypA cells. We determined the specific amino acid differences responsible and generated mutants able to fully rescue replication. We expressed these mutants in engineered murine hepatoma cells and although we observed increases in HCV replication following infection, they remained far lower than those in highly permissive human hepatoma cells, and minimal infectious particle release was observed. Together, these data suggest additional co-factors remain unidentified. Future work to determine such factors will be critical for developing an immunocompetent mouse model supporting HCV replication.
Publication Date: 10-May-2019
Electronic Publication Date: 10-May-2019
Citation: Gaska, Jenna M, Balev, Metodi, Ding, Qiang, Heller, Brigitte, Ploss, Alexander. (2019). Differences across cyclophilin A orthologs contribute to the host range restriction of hepatitis C virus.. eLife, 8 (10.7554/elife.44436
DOI: doi:10.7554/elife.44436
ISSN: 2050-084X
EISSN: 2050-084X
Pages: e44436
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: eLife
Version: Final published version. This is an open access article.

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