Journal
GASTROENTEROLOGY
Volume 147, Issue 5, Pages 1008-+Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2014.08.040
Keywords
RNA-Dependent RNA Polymerase; Virulence; Drug Resistant; Mechanism
Categories
Funding
- KU Leuven, geconcerteerde onderzoeksactie [GOA/10/014]
- EU [260644]
- Robert-Koch-Institute [1362-1097]
- German Federal Ministry for Education and Research [01E00802]
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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.
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