It is generally believed that miR-122, specifically expressed and highly abundant in the liver, facilitates replication of HCV. That is the reason why HCV RNA can only replicate in Huh7 cells, but not in HepG2 cells, which do not express endogenous miR-122 [
19].
In recent years, many studies have focused on the relationship between HCV and miR-122. There is, however, only limited information about the role of HCV in miR-122 expression. In our study, the intracellular levels of HCV RNA and miR-122 were measured at different time points after infecting with HCV. The results indicated that the level of HCV RNA increased rapidly during the infection, and there was a positive correlation between miR-122 level and HCV RNA level at the early stage of infection to some extent. However, in previous reports, no positive correlation was observed between miR-122 level and HCV [
22,
23]. It may be due to not strong correlation between miR-122 level and HCV RNA level or the different cell line. It was interesting that at day 19 after infection with HCV, there was an inverse correlation between miR-122 expression and HCV RNA expression, and miR-122 expression level was obviously reduced at the late stage of HCV infection. This inverse correlation between HCV and miR-122 was consistent with a previous in vitro study, which reported that miR-122 levels were significantly reduced on HCVcc infection [
24]. It was also found in our study that miR-122 expression level decreased in high-abundance HCV group. In a vivo experiment, a similar result was observed that the HCV subjects with higher viral load had lower miR-122 levels in liver than HCV subjects with lower viral load [
25]. Another similar result was published that hepatic miR-122 expression in serum HCV RNA-positive patients was significantly lower than that in serum HCV RNA-negative patients [
26]. Thus, it seemed that, with the accumulation of HCV, the inhibitory effect of HCV on miR-122 might be observed. Taken together, these results might support the notion that HCV monitors its replication by down-regulating the miR-122 level. Actually, a recently proposed hypothesis may provide a similar mechanistic explanation that, in order to survive, HCV need a steady viral replication rate [
27‐
30]. By keeping abundance relatively low, the virus evades the immune response of the host and establishes persistent chronic infection.
The subsequent results demonstrated that it was HCV core protein that suppressed miR-122 expression both in a time- and dose- dependent manner. And overexpression of HCV core protein did reduce the susceptibility of Huh7.5.1 cells to HCV, suggesting it might participate in the mechanism for self-regulation of HCV, which might be important for viral persistence. However, further studies are needed to address the precise mechanism by which core protein functions.