Study of cellular immune response against Hepatitis E Virus (HEV)

Prabhu, S. B.; Gupta, Priyanka; Durgapal, Hemlata; Rath, Satyajit; Gupta, Swati; Acharya, Subrat Kumar; Panda, Subrat Kumar

doi:10.1111/j.1365-2893.2010.01338.x

Cited by 64 publications

(68 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A study of the T Correlations were estimated by calculating Spearman's rank correlation coefficient. cells invading the liver during the acute phase of infection could confirm the hypothesis of impaired recruitment, since activated CD8 ϩ T cells were found recently in liver biopsy specimens from HEV-infected patients (29).…”

Section: Discussionsupporting

confidence: 55%

Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

Lhomme

Abravanel

Dubois

et al. 2012

J Virol

View full text Add to dashboard Cite

c 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.

show abstract

Section: Discussionsupporting

confidence: 55%

Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

Lhomme

Abravanel

Dubois

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…In a recent report, when post mortem liver biopsies from HEV-ALF patients were evaluated to identify the type of cellular infiltrate, it was seen that activated CD8 CTL (Granzyme +ve, perforin +ve) were markedly higher in liver tissues of such patients than in the liver tissue of healthy control liver (collected intraoperatively during cholecystectomy) and were similar to such infiltrate in HBV-ALF, a known model of Th1 mediated immune injury to liver. 63 Further, CTL epitopes have been documented against both ORF2 and ORF3 of HEV genomes in in-vitro studies. 64 In human studies which include HEV infected pregnant females, a decrease in peripheral CD4 count with increase in CD8 count and altered CD4/ CD8 ratio have been documented.…”

Section: Malnutritionmentioning

confidence: 99%

Hepatitis E and Acute Liver Failure in Pregnancy

Shalimar

Acharya

2013

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

“…Prabhu et al (2010), more specifically demonstrated the involvement of activated CD8+ T-cells containing granzymes in acute live failure cases of HEV infection. 18 The absence of Treg cells in HEV infected liver tissues suggests that no regulation of immune mediated killing during HEV infection might be associated with severity of the disease. À Foxp3 + T (Effector Treg) cells in acute hepatitis E patients were significantly higher compared to controls and recovered individuals.…”

Section: Pathogenesismentioning

confidence: 99%

“…84 HEV antigens were detected in the hepatocytes of infected patients and experimentally infected animals. 18,85 The presence of negative-strand HEV RNA replicative intermediates in the liver of infected rhesus monkeys constituted the first direct evidence of HEV replication in the liver. 7 There is also evidence of extrahepatic replication of HEV like the biliary epithelial cells in rhesus monkeys.…”

Section: Replication Cyclementioning

confidence: 99%

“…However, a wide body of clinical, immunopathological and histopathological studies helped in identifying the stages of infection and the hallmark immune mediated disease outcome, similar to other viral hepatitis. 17,18 HEV pathogenesis varies, from being asymptomatic or acute, self-limiting in low risk groups to causing chronic and/ or fulminant hepatic failure in high risk groups; the modus operandi remains hypothetical. Increasing reports typify route, establishment and pathogenic outcome during hepatitis E infection to host factors and genotype involved.…”

Section: Thementioning

confidence: 99%

See 1 more Smart Citation

Hepatitis E: Molecular Virology and Pathogenesis

Panda

Varma

2013

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus classified under the family Hepeviridae. Enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of HEV made it to be a less understood agent. Early studies on animal models, sub-genomic expression of open reading frames (ORF) and infectious cDNA clones have helped in elucidating the genome organization, important stages in HEV replication and pathogenesis. The genome contains three ORF's and three untranslated regions (UTR). The 5 0 distal ORF, ORF1 is translated by host ribosomes in a cap dependent manner to form the non-structural polyprotein including the viral replicase. HEV replicates via a negative-sense RNA intermediate which helps in the formation of the positive-sense genomic RNA and a single bi-cistronic sub-genomic RNA. The 3 0 distal ORF's including the major structural protein pORF2 and the multifunctional host interacting protein pORF3 are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not well articulated, and remains a concern due to the many aspects like host dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in immunosuppressed patients, and rapid decompensation in affected chronic liver diseased patients warrants detailed investigation of the underlying pathogenesis. Recent advances about structure, entry, egress and functional characterization of ORF1 domains has furthered our understanding about HEV. This article is an effort to review our present understanding about molecular biology and pathogenesis of HEV. ( J CLIN EXP HEPATOL 2013;3:114-124) H epatitis E virus was first identified in 1983 as the agent responsible for the large scale waterborne epidemics of acute, self-limiting hepatitis in developing nations.1 It was shown to be a naked 28-34 nm virus-like particle with spikes and inundations. 1,2Successful use of non-human primate models for HEV propagation helped in its isolation, cloning and sequencing and as presumed turned out to be an RNA virus.3,4 It had a $7.2 kb single stranded genome with sequence homology to other positive-sense RNA viruses. 4,5 Computer based genome annotation revealed three overlapping open reading frames ORF1, ORF2 and ORF3.4,5 The longest ORF, ORF1 formed the 5 0 distal end of the genome and coded for the non-structural replication proteins including methyltransferase, protease, helicase, and RNA dependent RNA polymerase (RdRp). The 30 distal ORF, ORF2 coded for an arginine rich protein, together with immunodominant sero-reactivity and agglutination against the expressed epitopes, it was predicted to be the major structural protein. A third ORF, ORF3 coded for a small protein thought to be a minor structural protein. [4][5][6] Molecular characterization and replication model of HEV remained...

show abstract

Study of cellular immune response against Hepatitis E Virus (HEV)

Cited by 64 publications

References 29 publications

Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

Hepatitis E and Acute Liver Failure in Pregnancy

Hepatitis E: Molecular Virology and Pathogenesis

Contact Info

Product

Resources

About