Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes

ABSTRACT: Long term cell culture adaptation of hepatitis C virus resulted in increased replication fitness in various human liver cell lines but in a moderate decrease in virus particle production upon infection of primary human hepatocytes (PHH). In order to identify molecular mechanisms conferring phenotypic differences in replicative fitness of the cell culture adapted virus strain p100pop, we infected PHH and Huh-7 cells with HCV, using the cell culture adapted strain p100pop or a Jc1 strain with similar genome organisation (Jc1-SP). Total RNA was extracted at 28 hours post inoculation and used for RNA sequencing. Transcriptome analyses, gene ontology enrichment analyses and KEGG pathway analyses revealed strong differences in the transcriptional signature of infected hepatoma cells and primary hepatocytes and the two virus strains used in this study. Wheras an innate immune response was induced in primary cells regardless of the infecting virus strain, this was not detectable in Huh-7 cells. Even though both viruses induce a similar host response in primary cells, the data indicate that the presence of cell culture adaptive mutations results in an increased expression of genes involved in the defense response to viral infection. In Huh-7 cells, differentially expressed genes associated with ER stress and apoptosis were solely enhanced upon p100pop infection but not upon Jc1-SP infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246981 | GEO | 2024/01/19

REPOSITORIES: GEO