RESUMEN
In this study we used the newly immortalized primary hepatocyte cell line called HuSE7/DN24 [HuS] to establish an in vitro infection and replication system for HCV genotype 4 [HCV-4a]. HuS cells were infected with sera obtained from Egyptian patients with chronic hepatitis C genotype 4a. HCV-4a could infect HuS cells in a dose dependent manner. HuS cells were permissive for HCV-4a infection and replication by 8 - 20 folds higher than that noticed in Huh 7.5 cells under the same infection conditions. Comparing the infectivity and replication of the HCV-4a from different Egyptian sera with that of HCV-1b from Japanese serum showed that HCV-4a is replicating in HuS cells 5 - 7 times better than HCV-1b under similar infection conditions. The HCV-4a replication in HuS cells was detectable after 3 days of culture, peaked after 5 days and then declined at day 7 of culture. The HCV-4a infection and replication in HuS cells could be completely inhibited by Cyclosporine [CsA] in a concentration of 3 micro g/ml of the culture medium. NIM811 which is a nonimmunosuppressive derivative of CsA could further inhibit HCV-4a infection and replication in HuS cells when added in a concentration of 0.5 micro g/ml of the culture medium. Meanwhile, IFN? in a dose of 50U/ml in culture medium could inhibit HCV-4a replication in HuS cells by more than 90%. This study may be the first ex-vivo study examining the infectivity and replication of HCV-4a in primary hepatocytes. Also, it is the first study examining the effect of cyclosporine and NIM811 on HCV-4a infection and replication in primary hepatocytes in vitro