The expression of HCV-associated host factors is dependent on the hepatoma cell line used in HCV studies

Abstract

Chronic infection by hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. At present, the most commonly used in vitro model of HCV infection is based on hepatoma cell lines. However, they were obtained from different patients and different cancers and/or differ in their characteristics and permissiveness to HCV. HCV infection can be modulated by several host factors, so we compared six different hepatoma cell lines that are used as in vitro models for HCV for some of these host factors: the seven known HCV entry factors, the six best-characterized HCV-associated microRNAs, and the two single-nucleotide polymorphisms near the IL28B gene associated with response to pegylated alpha interferon and ribavirin combination therapy, all assessed by quantitative PCR. We showed that the cell lines, including Huh-7 and Huh-7-derived cells, have different microRNA and HCV entry factor expression profiles as well as different IL28B genotypes. In conclusion, some of the observed differences might explain the differences in permissiveness of the cell lines, but, above all, they raise questions about the reliability of in vitro HCV research data gathered to date.

MicroRNA-Related Polymorphisms in Infectious Diseases—Tiny Changes With a Huge Impact on Viral Infections and Potential Clinical Applications

“…Moreover, evaluation HCV-infected patients, Su et al ( 90 ) found an association between TT genotype of IFNL4/IL28B rs8099917 and high levels of serum miR-122. In agreement with results from population studies, an in vitro assay suggested that both IFNL4/IL28B rs12979860 and IFNL4/IL28B rs8099917 modulate the course of HCV infection, although how exactly this modulation happens is still not understood ( 87 ). However, as often is the case, there are conflicting data from studies that do not corroborate these associations ( 88 , 91 , 92 ).…”

“…MiR-122 is abundantly expressed in hepatic cells ( 85 – 87 ) and markedly influences the clinical course of HCV infection ( 86 , 88 ). Some attempts to explain this influence have focused on genetic variants that affect miR-122 expression.…”

Inhibition of hepatitis C virus RNA replication by ISG15 does not require its conjugation to protein substrates by the HERC5 E3 ligase

“…Given the different approaches used by various groups to determine whether ISG15 affects HCV replication, it is difficult to reconcile all available data. Moreover, Huh7 cells and their derivatives are highly heterogeneous and therefore may influence the observed phenotypes ( Bensadoun et al , 2011 ; Hoffmann et al , 2014 ). Consequently, we selected U2OS cells as an alternative line that supports HCV RNA replication ( Targett-Adams & McLauchlan, 2005 ) to validate our findings.…”

Anti-lipopolysaccharide factor isoform 3 from Penaeus monodon (ALFPm3) exhibits antiviral activity by interacting with WSSV structural proteins

“…The antiviral activity of ALF derivatives has also been reported, where the cyclic synthetic fragment of ALF exhibited antiviral activity against nervous necrosis virus (NNV), a fish non-enveloped viral pathogen, by agglutinating the NNV virions (Chia et al, 2010). In addition, a synthetic ALF based on the LPS-binding domain of Limulus ALF blocked the viral entry of various human pathogenic viruses, such as HIV-1, HCV and HSV1 and 2, by binding to the docking molecule on the host cell surface (Krepstakies et al, 2012;Hoffmann et al, 2014). However, the antiviral mechanism(s) of ALF against WSSV are not understood.…”