43 HCV is known to exploit autophagy for its replication,44 and inhibition of replication by CQ targets virus-associated autophagy.43 However, it
remains to be determined whether inhibition of HCV RNA replication by FQ depends on the same mechanism. In clinical studies with healthy human volunteers, it has been shown that FQ is safe and very well tolerated with oral doses of 400-1,600 mg FQ, and the mean estimate for blood apparent terminal half-life of FQ was 16 days.45 In addition, a maximum blood concentration of 487 ng/mL (or 1.1 μM) was observed for the highest dose of FQ, which is slightly above the IC50 value calculated for HCV in cell culture. Although such a concentration would probably not be high enough to eliminate HCV selleck compound completely, it would likely be
sufficient in combination therapies with other drugs showing a synergistic or additive effect. Further studies will be necessary to determine the in vivo potency of FQ against HCV. FQ may provide a new Palbociclib datasheet approach to prevent HCV infection, especially in the setting of liver transplantation (LT) of chronically infected HCV patients. Indeed, a major problem for LT resulting from HCV is the reinfection of the graft, which is always observed with an accelerated progression of liver disease.46 Thus, the ability of FQ at inhibiting HCV cell-to-cell transmission is a major asset for an entry inhibitor. Furthermore, FQ exhibits an antiviral activity against all HCV genotypes, tested in the HCVpp system, increasing its potential interest as a general anti-HCV agent. find more The combination of entry, replication, and polyprotein-processing inhibitors in a context of a multidrug therapy might be the way to reduce the risk of emergence of resistant viruses. FQ might thus be a valuable option to be tested in low-cost anti-HCV combinations. Finally, these findings highlight the potential interest of FQ use in
countries where malaria coinfection with HCV can occur. The authors thank Julie Potel, Yves Rouillé, and Karin Séron for their scientific input. Additional Supporting Information may be found in the online version of this article. “
“Aim: The aim of the present study was to quantitatively monitor the response of CD95 molecules expressed on CD3+ T cells (CD95+CD3+ cells) and CD38 molecules expressed on CD8+ T cells (CD38+CD8+ cells) to ganciclovir treatment after orthotopic liver transplant (OLT) in recipients with active human cytomegalovirus (HCMV) infection. Methods: Blood samples were collected from 20 liver transplanted recipients with active HCMV infection and 24 recipients without HCMV infection. CD95+CD3+ cells and CD38+CD8+ cells were quantitatively detected with QuantiBRITE bead methods by dual-color flow cytometry analysis during the post-transplantation period. Results: CD95+CD3+ cells and CD38+CD8+ cells were not significantly different among different ages of healthy adults (P > 0.05).