An Analysis of the Benefit of Using HEV Genotype 3 Antigens in Detecting Anti-HEV IgG in a European Population

Annatina Schnegg,Alain Kenfak-Foguena,Philippe Bürgisser,Matthias Cavassini,Florence Abravanel,Darius Moradpour,Giorgia Canellini,Cyril André,Jacques Izopet,Katharine E A Darling

doi:10.1371/journal.pone.0062980

Abstract

BackgroundThe benefit of using serological assays based on HEV genotype 3 in industrialised settings is unclear. We compared the performance of serological kits based on antigens from different HEV genotypes.MethodsTaking 20 serum samples from patients in southwest France with acute HEV infection (positive PCR for HEV genotype 3) and 550 anonymised samples from blood donors in southwest Switzerland, we tested for anti-HEV IgG using three enzyme immunoassays (EIAs) (MP Diagnostics, Dia.Pro and Fortress) based on genotype 1 and 2 antigens, and one immunodot assay (Mikrogen Diagnostik recomLine HEV IgG/IgM) based on genotype 1 and 3 antigens.ResultsAll acute HEV samples and 124/550 blood donor samples were positive with ≥1 assay. Of PCR-confirmed patient samples, 45%, 65%, 95% and 55% were positive with MP Diagnostics, Dia.Pro, Fortress and recomLine, respectively. Of blood donor samples positive with ≥1 assay, 120/124 (97%), were positive with Fortress, 19/124 (15%) were positive with all EIAs and 51/124 (41%) were positive with recomLine. Of 11/20 patient samples positive with recomLine, stronger reactivity for HEV genotype 3 was observed in 1/11(9%), and equal reactivity for both genotypes in 5/11 (45.5%).ConclusionsAlthough recomLine contains HEV genotype 3, it has lower sensitivity than Fortress in acute HEV infection and fails to identify infection as being due to this genotype in approximately 45% of patients. In our single blood donor population, we observe wide variations in measured seroprevalence, from 4.2% to 21.8%, depending on the assay used.

Highlights

Hepatitis E virus (HEV) is a single-stranded RNA virus acquired predominantly through faeco-oral transmission
Of the four HEV genotypes linked to human infection, outbreaks are generally caused by genotype 1 or 2, whilst genotype 3 is associated with autochthonous infection in humans, pigs and other mammals [2,3,4]
Assay sensitivity varies between different kits, for several reasons: assays for HEV antibodies based on recombinant proteins have been found to be more sensitive than those based on synthetic peptides [9]; antigenic properties of the epitopes, especially those of ORF2, are strongly conformationdependent; and HEV sequence heterogeneity implies that antibody epitopes may not be conserved across strains

Summary

Introduction

Hepatitis E virus (HEV) is a single-stranded RNA virus acquired predominantly through faeco-oral transmission. Identified as a virus endemic in low-income regions, causing waterborne outbreaks of hepatitis, HEV is recognised as the agent of a zoonotic infection, causing indigenous disease in industrialised countries [1]. Anti-HEV IgM and IgG are detectable at symptom onset, if symptoms occur. The assays are based on proteins derived from two of the three open reading frames (ORFs) contained in the HEV genome, ORF2 and ORF3. The observation that certain serological tests have higher sensitivity for genotype 1 than for genotype 3 [2] suggests that anti-HEV IgG screening in industrialised countries, where indigenous infection is with genotype 3, is potentially hampered. The benefit of using serological assays based on HEV genotype 3 in industrialised settings is unclear. We compared the performance of serological kits based on antigens from different HEV genotypes

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