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

• DOI: 10.7554/elife.44436
• Publication Date: 2019-05-07T14:00:35Z
• Authors: Jenna M Gaska; Metodi Balev; Qiang Ding; Brigitte Heller; Alexander Ploss
• Keywords: Cypa; Host factors; Tissue tropism; Permissive

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 machinery orthologs essential factors, like cyclophilin A (CypA). We thus compared ability CypA from mouse, tree shrew, seven non-human primate to support replication, finding that murine only partially rescued Huh7.5-shRNA cells. determined specific amino acid differences responsible generated mutants able fully rescue replication. expressed these engineered hepatoma cells although we observed increases following infection, they remained far lower than those highly permissive human cells, minimal infectious particle release was observed. Together, data suggest additional co-factors remain unidentified. Future work determine such factors will critical for immunocompetent mouse model supporting