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

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• 作者：Yannick Debing¹ ; ^&lowast ; ; Anett Gisa² ; ^&lowast ; ; Kai Dallmeier¹ ; Sven Pischke³ ; Birgit Bremer² ; Michael Manns² ; Heiner Wedemeyer² ; ^§ ; ; Pothakamuri Venkata Suneetha² ; ^§ ; ; Johan Neyts¹ ; ^{johan.neyts@rega.kuleuven.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：RNA-Dependent RNA Polymerase ; Virulence ; Drug Resistant ; Mechanism
• 刊名：Gastroenterology
• 出版年：2014
• 出版时间：November 2014
• 年：2014
• 卷：147
• 期：5
• 页码：1008-1011.e7
• 全文大小：1338 K

文摘

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.