Abstract
Hepatitis E virus (HEV) is a human pathogen with increasing importance. The lack of efficient cell culture systems hampers systematic studies on its replication cycle, virus neutralization and inactivation. Here, several cell lines were inoculated with the HEV genotype 3c strain 47832c, previously isolated from a chronically infected transplant patient. At 14 days after inoculation the highest HEV genome copy numbers were found in A549 cells, followed by PLC/PRF/5 cells, whereas HepG2/C3A, Huh-7 Lunet BLR and MRC-5 cells only weakly supported virus replication. Inoculation of A549-derived subclone cell lines resulted in most cases in reduced HEV replication. However, the subclone A549/D3 was susceptible to lower virus concentrations and resulted in higher virus yields as compared to parental A549 cells. Transcriptome analysis indicated a downregulation of genes for carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 5 and 6, and an upregulation of the syndecan 2 (SDC2) gene in A549/D3 cells compared to A549 cells. However, treatment of A549/D3 cells or A549 cells with CEACAM- or syndecan 2-specific antisera did not influence HEV replication. The results show that cells supporting more efficient HEV replication can be selected from the A549 cell line. The specific mechanisms responsible for the enhanced replication remain unknown.
Highlights
Hepatitis E virus (HEV) is the causative agent of acute hepatitis in humans
The human liver carcinoma cell lines PLC/PRF/5, HepG2/C3A and Huh-7 Lunet BLR, as well as the lung fibroblast cell line MRC-5 and the human lung carcinoma cell line A549 were inoculated with the HEV strain 47832c
A549 cells were selected for further experiments to optimize the HEV cell culture system
Summary
Hepatitis E virus (HEV) is the causative agent of acute hepatitis in humans. It causes worldwide an estimated 20 million cases and 56,000 deaths every year [1]. Most of the cases occur in developing countries where the virus is mainly transmitted by fecally contaminated drinking water. Hepatitis E cases are increasingly recognized in industrial countries where HEV is mostly zoonotically transmitted from pigs and wild boars [2]. Chronic HEV infections of immunosuppressed transplant patients, which may cause liver cirrhosis, have been increasingly reported [3]. HEV particles are icosahedral and non-enveloped, recent analyses of cell culture-derived
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