A Mutation in the Hepatitis E Virus RNA Polymerase Promotes Its Replication and Associates With Ribavirin Treatment Failure in Organ Transplant Recipients

作者：Debing Yannick; Gisa Anett; Dallmeier Kai; Pischke Sven; Bremer Birgit; Manns Michael; Wedemeyer Heiner; Suneetha Pothakamuri Venkata; Neyts Johan^*

来源：Gastroenterology, 2014, 147(5): 1008-+.

DOI：10.1053/j.gastro.2014.08.040

• RNA-Dependent RNA Polymerase
• Virulence
• Drug Resistant
• Mechanism

We analyzed blood samples collected from 15 patients with chronic hepatitis E who were recipients of solid-organ transplants. All patients cleared the hepatitis E virus (HEV) except for 2 (nonresponders); 1 patient died. A G1634R mutation in viral polymerase was detected in the HEV RNA of the nonresponders; this mutation did not provide the virus with resistance to ribavirin in vitro. However, the mutant form of a subgenomic replicon of genotype 3 HEV replicated more efficiently in vitro than HEV without this mutation, and the same was true for infectious virus, including in competition assays. Similar results were obtained for genotype 1 HEV. The G1634R mutation therefore appears to increase the replicative capacity of HEV in the human liver and hence reduce the efficacy of ribavirin.

• 出版日期2014-11
• 单位河北医科大学