TY - JOUR
T1 - Increased replicative fitness can lead to decreased drug sensitivity of hepatitis C virus
AU - Sheldon, Julie
AU - Beach, Nathan M.
AU - Moreno, Elena
AU - Gallego, Isabel
AU - Piñeiro, David
AU - Martínez-Salas, Encarnación
AU - Gregori, Josep
AU - Quer, Josep
AU - Esteban, Juan Ignacio
AU - Rice, Charles M.
AU - Domingo, Esteban
AU - Peralesa, Celia
PY - 2014/1/1
Y1 - 2014/1/1
N2 - © 2014, American Society for Microbiology. Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV.
AB - © 2014, American Society for Microbiology. Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV.
U2 - 10.1128/JVI.01860-14
DO - 10.1128/JVI.01860-14
M3 - Article
VL - 88
SP - 12098
EP - 12111
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 20
ER -