In vitro infection of immortalized primary hepatocytes by HCV genotype 4a and inhibition of virus replication by cyclosporin.

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma worldwide. We previously reported that cyclosporin A (CsA) inhibits HCV-1b replication. However, its inhibition of JFH-1 (HCV-2a) was much less. Since HCV genotype clearly affects the in vitro and in vivo response to anti-viral therapy, we wished to examine the effect of CsA and its non-immunosuppressive derivative NIM811 on HCV genotype 4a replication. We first established an in vitro system supporting HCV-4a infection and replication using immortalized human hepatocytes, HuS-E7/DN24 (HuS) cells, and these cells were infected with sera obtained from Egyptian patients with chronic HCV-4a infection. HuS cells supported more robust HCV-4a replication than both HuH-7.5 and PH5CH8 cells, and HCV-4a infection and replication were completely inhibited by 3 mug/ml CsA and 0.5 mug/ml NIM811. Thus, HuS cells are a good model system supporting the infection and high-level replication of HCV-4a, and both CsA and NIM811 effectively inhibit HCV-4a replication in this system.

Allopurinol as a potential therapeutic agent for recurrent herpes labialis.

Recurrent herpes labialis (RHL) occurs in up to 40% of the population. Although the disease is usually self-limiting, patients seek treatment because of the significant pain and visibility of the lesion. Xanthine oxidase inhibitors (XOI) have been reported to have a potent antiviral effect against influenza-A virus. We examined the effect of the systemic xanthine oxidase inhibitor, allopurinol, on RHL duration of illness, severity of symptoms, number and frequency of recurrence during a 4-year follow up period in Egyptian patients. Duration of illness was shortened by about 25%, early disappearance of pain and other symptoms occurred. Also, aborted episodes were noticed when allopurinol was given just after beginning of common colds, at the prodromal stage of RHL or during severe stress conditions. Patients receiving 3 courses of treatment had markedly decreased recurrences during the follow up period. Ex vivo experiments to examine virus-induced plaque formation on Vero cells in the absence or presence of different concentrations of the drug could not prove any direct anti herpetic effect of the drug. However, allopurinol seems to be safe and effective in reducing duration of RHL and to abort lesion or prevent its appearance in treated patients even when they experience immunosuppressive conditions.