Hepatitis C virus infection dynamics, treatment, and lipid nanoparticle-mediated infection in humanized liver chimeric mouse models - PubMed
4 hours ago
- #Lipid Nanoparticles
- #Hepatitis C Virus
- #Mouse Models
- The study highlights the utility of humanized liver chimeric mouse models (FRG and uPA-SCID) for HCV research, including infection dynamics and antiviral testing.
- Mice engrafted with primary human hepatocytes developed high-level viremia (up to 10^8 copies/mL) when inoculated with HCV-positive serum or lipid nanoparticle (LNP)-encapsulated HCV RNA, with RNA-LNP infection mirroring serum-derived infection and being transmissible.
- Treatment with glecaprevir/pibrentasvir cleared HCV viremia in the mice, and treated mice could be reinfected, demonstrating the model's applicability for studying treatment outcomes.
- The proportion of antibody-free HCV RNA in human serum correlated with infectivity, suggesting a role in infection dynamics.
- LNP-based RNA delivery is presented as a scalable approach for generating standardized challenge inocula for HCV research.