title: Hepatitis E virus quasispecies and the outcome of acute hepatitis E in solid-organ transplant patients.
abstract: Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lower K(a)/K(s) ratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.
authors: INSERM, UMR1043, Toulouse, France.
authors: Sebastien
authors: S
authors: Lhomme
authors: Florence
authors: F
authors: Abravanel
authors: Martine
authors: M
authors: Dubois
authors: Karine
authors: K
authors: Sandres-Saune
authors: Lionel
authors: L
authors: Rostaing
authors: Nassim
authors: N
authors: Kamar
authors: Jacques
authors: J
authors: Izopet
mesh_terms: D000328:Adult; D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D016751:Hepatitis E / Q000209:etiology* / Q000276:immunology / Q000821:virology*; D016752:Hepatitis E virus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D016867:Immunocompromised Host; D008103:Liver Cirrhosis / Q000209:etiology / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016377:Organ Transplantation / Q000009:adverse effects*; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics
chemical_list: D036022:Capsid Proteins; D018925:Chemokines; D016207:Cytokines; C400971:ORF2 protein, Hepatitis E virus; D012367:RNA, Viral; D014764:Viral Proteins