Variability and pathogenicity of hepatitis E virus genotype 3 variants.
Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype.
University of Edinburgh, CIIE, Ashworth Laboratories, King's Buildings, Edinburgh EH9 3FL, UK.
Donald B
DB
Smith
Blood Borne Virus Unit, Virus Reference Department, MS-Colindale, Public Health England, London NW9 5EQ, UK.
Samreen
S
Ijaz
Blood Borne Virus Unit, Virus Reference Department, MS-Colindale, Public Health England, London NW9 5EQ, UK.|University College London, Gower Street, London WC1E 6BT, UK.
Richard S
RS
Tedder
Department of Blood-borne Infections, Sanquin Research, PO Box 9190, 1006 AD Amsterdam, The Netherlands.
Boris
B
Hogema
Department of Blood-borne Infections, Sanquin Research, PO Box 9190, 1006 AD Amsterdam, The Netherlands.
Hans L
HL
Zaaijer
Institut National de la Sante et de la Recherche Medicale Unite 1043, Toulouse, France.
Jacques
J
Izopet
West of Scotland Specialist Virology Centre, New Lister Building, Glasgow, UK.
Amanda
A
Bradley-Stewart
West of Scotland Specialist Virology Centre, New Lister Building, Glasgow, UK.
Rory
R
Gunson
Specialist Virology Centre, Royal Infirmary of Edinburgh, UK.|Public Health Agency of Sweden (previously Swedish Institute for Communicable Disease Control), Solna, Sweden.|European Programme for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden.
Heli
H
Harvala
Specialist Virology Centre, Royal Infirmary of Edinburgh, UK.
Inka
I
Kokki
University of Edinburgh, Roslin Institute, Easter Bush, Edinburgh EH25 9RG, UK.
Peter
P
Simmonds
D005602:France; D014644:Genetic Variation; D005858:Germany; D016751:Hepatitis E / Q000821:virology*; D016752:Hepatitis E virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009426:Netherlands; D010802:Phylogeny; D012606:Scotland; D014774:Virulence