Mosimann, A. L. P. | bioRxiv Science

bioRxiv2025

An immunocompetent murine model of virus-elicited liver fibrosis and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third deadliest cancer worldwide. Over 75% of HCC cases are associated with chronic viral infections. Mechanistic studies and preclinical therapeutic development for virus-associated HCC have been limited by a paucity of small animal models of chronic hepatotropic virus infection that faithfully recapitulate human disease. Here we demonstrate the induction of chronic hepatitis, progressive liver fibrosis, and HCC in immunocompetent laboratory mice upon chronic viral infection with Norway rat hepacivirus (NrHV) - a virus closely related to hepatitis C virus (HCV). NrHV-elicited tumors resemble HCV-associated tumors and liver transcriptome analyses reveal numerous similarities between chronic NrHV and HCV. These findings establish an experimentally tractable, physiologically relevant, and immunocompetent mouse model of virus-elicited progressive liver fibrosis and oncogenesis.

pathology↗

bioRxiv2021

Human neutrophils are not activated by Zika virus but reduce the infection of susceptible cells

Zika virus (ZIKV) emergence highlighted the need for a deeper understanding on virus-host interaction to pave the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are an important effector cell in innate immunity involved in the host response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strains replication. Indeed, after stimulation with ZIKV, neutrophils were not primed against the virus as evaluated by the absence of CD11b modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, ZIKV infection of primary innate immune cells in vitro did not trigger neutrophil migration. However, neutrophil co-cultured with ZIKV susceptible cells (A549) resulted in lower frequencies of infection on A549 cells by cell-to-cell contact. In vivo, neutrophil depletion from immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest human neutrophils do not play a per se antiviral role against ZIKV, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.

immunology↗