scholarly journals Effector memory CD8 T cell response elicits Hepatitis E Virus genotype 3 pathogenesis in the elderly

2021 ◽  
Vol 17 (2) ◽  
pp. e1009367
Author(s):  
Hicham El Costa ◽  
Jordi Gouilly ◽  
Florence Abravanel ◽  
Elmostafa Bahraoui ◽  
Jean-Marie Peron ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Hepatitis E Virus ◽  
Clinical Symptoms ◽  
Hepatitis E ◽  
Effector Memory ◽  
Elderly Subjects ◽  
Antigen Specificity ◽  
Genotype 3

Genotype 3 Hepatitis E virus (HEV-3) is an emerging threat for aging population. More than one third of older infected patients develops clinical symptoms with severe liver damage, while others remain asymptomatic. The origin of this discrepancy is still elusive although HEV-3 pathogenesis appears to be immune-mediated. Therefore, we investigated the role of CD8 T cells in the outcome of the infection in immunocompetent elderly subjects. We enrolled twenty two HEV-3-infected patients displaying similar viral determinants and fifteen healthy donors. Among the infected group, sixteen patients experienced clinical symptoms related to liver disease while six remained asymptomatic. Here we report that symptomatic infection is characterized by an expansion of highly activated effector memory CD8 T (EM) cells, regardless of antigen specificity. This robust activation is associated with key features of early T cell exhaustion including a loss in polyfunctional type-1 cytokine production and partial commitment to type-2 cells. In addition, we show that bystander activation of EM cells seems to be dependent on the inflammatory cytokines IL-15 and IL-18, and is supported by an upregulation of the activating receptor NKG2D and an exuberant expression of T-Bet and T-Bet-regulated genes including granzyme B and CXCR3. We also show that the inflammatory chemokines CXCL9-10 are increased in symptomatic patients thereby fostering the recruitment of highly cytotoxic EM cells into the liver in a CXCR3-dependent manner. Finally, we find that the EM-biased immune response returns to homeostasis following viral clearance and disease resolution, further linking the EM cells response to viral burden. Conversely, asymptomatic patients are endowed with low-to-moderate EM cell response. In summary, our findings define immune correlates that contribute to HEV-3 pathogenesis and emphasize the central role of EM cells in governing the outcome of the infection.

scholarly journals Hepatitis E virus-specific T-cell response after transplantation

Hepatology ◽  
2012 ◽  
Vol 55 (5) ◽  
pp. 1643-1643 ◽  
Author(s):  
Nassim Kamar ◽  
Florence Legrand-Abravanel ◽  
Harry R. Dalton ◽  
Jacques Izopet
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
T Cell Response

Characterization of the HEV-specific CD8 T-cell response in acute and chronic Hepatitis E virus infection

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
J Kemming ◽  
M Panning ◽  
S Pischke ◽  
J Schulze zur Wiesch ◽  
M Lütgehetmann ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
T Cell ◽  
Virus Infection ◽  
Cell Response ◽  
Hepatitis E Virus ◽  
Cd8 T Cell ◽  
Hepatitis E ◽  
T Cell Response ◽  
Acute And Chronic Hepatitis

Characterization of the HEV-specific CD8+ T-cell response in acute and chronic hepatitis E virus infection

2018 ◽  
Vol 68 ◽  
pp. S800
Author(s):  
J. Kemming ◽  
M. Panning ◽  
M. Luetgehetmann ◽  
S. Pischke ◽  
J.S.Z. Wiesch ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
T Cell ◽  
Virus Infection ◽  
Cell Response ◽  
Hepatitis E Virus ◽  
Cd8 T Cell ◽  
Hepatitis E ◽  
T Cell Response ◽  
Acute And Chronic Hepatitis

scholarly journals Advances in Hepatitis E Virus Biology and Pathogenesis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 267
Author(s):  
Shaoli Lin ◽  
Yan-Jin Zhang
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Case Fatality ◽  
Hepatitis E ◽  
Host Cells ◽  
High Rate ◽  
Rapid Progression ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Zoonotic Infections

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

scholarly journals Epidemiology of Hepatitis E in 2017 in Bavaria, Germany

2021 ◽  
Author(s):  
K. Hriskova ◽  
D. Marosevic ◽  
A. Belting ◽  
J. J. Wenzel ◽  
A. Carl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis E ◽  
Food Samples ◽  
Healthy Population ◽  
Genotype 3 ◽  
Human Samples ◽  
Multivariable Analyses ◽  
Upper Abdominal ◽  
Undercooked Meat

AbstractIn the last decade, the number of reported hepatitis E virus (HEV) infections in Germany, including Bavaria, has continued to rise. In order to identify risk factors associated with HEV infection, we investigated notified hepatitis E cases from Bavaria during 2017. The project “Intensified Hepatitis E Surveillance in Bavaria” included interviews with questionnaires, collection and genotyping of stool, serum and food samples. In addition, certain risk factors were examined in a sample comparison with healthy population using univariable analysis and logistic regression. In total, 135 hepatitis E cases from Bavaria were included in the analysis. Mean age for women was 46 (range 20–74) years and 47.5 (range 20–85) for men. 56 of the cases (41.5%) were asymptomatic. Among the symptomatic cases, both men and women were equally affected with symptoms like fever (16.3%), jaundice (18.8%) and upper abdominal pain (28.2%). 145 human samples (serum, stool) and 6 food samples were collected. 15.9% of the human samples (n = 23) were positive for HEV RNA by reverse-transcription quantitative real-time PCR (RT-qPCR). Identified risk factors significantly associated with hepatitis E were sausage consumption with odds ratio 9.6 (CI 1.3–70.1), fish with OR 2.2 (CI 1.1–4.4) and cat ownership with OR 1.9 (CI 1.3–3.0) in multivariable analyses. Further investigation is needed to confirm the role of fish in HEV transmission. Autochthonous HEV genotype 3 is prevalent in Bavaria and there could be more transmission routes contributing to the spread of HEV than previously known. Undercooked meat, offal, sausages, fish, shellfish and contact with animals and pets are possible sources for infection.

scholarly journals Infection dynamics and persistence of hepatitis E virus on pig farms – a review

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
M. Meester ◽  
T. J. Tobias ◽  
M. Bouwknegt ◽  
N. E. Kusters ◽  
J. A. Stegeman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis E Virus ◽  
Risk Mitigation ◽  
Transmission Rate ◽  
Hepatitis E ◽  
Main Body ◽  
Genotype 3 ◽  
Infection Dynamics ◽  
Pig Farms ◽  
Slaughter Pigs

Abstract Background Hepatitis E virus (HEV) genotype 3 and 4 is a zoonosis that causes hepatitis in humans. Humans can become infected by consumption of pork or contact with pigs. Pigs are the main reservoir of the virus worldwide and the virus is present on most pig farms. Main body Though HEV is present on most farms, the proportion of infected pigs at slaughter and thus the level of exposure to consumers differs between farms and countries. Understanding the cause of that difference is necessary to install effective measures to lower HEV in pigs at slaughter. Here, HEV studies are reviewed that include infection dynamics of HEV in pigs and on farms, risk factors for HEV farm prevalence, and that describe mechanisms and sources that could generate persistence on farms. Most pigs become infected after maternal immunity has waned, at the end of the nursing or beginning of the fattening phase. Risk factors increasing the likelihood of a high farm prevalence or proportion of actively infected slaughter pigs comprise of factors such as farm demographics, internal and external biosecurity and immunomodulating coinfections. On-farm persistence of HEV is plausible, because of a high transmission rate and a constant influx of susceptible pigs. Environmental sources of HEV that enhance persistence are contaminated manure storages, water and fomites. Conclusion As HEV is persistently present on most pig farms, current risk mitigation should focus on lowering transmission within farms, especially between farm compartments. Yet, one should be aware of the paradox of increasing the proportion of actively infected pigs at slaughter by reducing transmission insufficiently. Vaccination of pigs may aid HEV control in the future.

scholarly journals Hepatitis E Virus Occurrence in Pigs Slaughtered in Italy

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 277
Author(s):  
Eleonora Chelli ◽  
Elisabetta Suffredini ◽  
Paola De Santis ◽  
Dario De Medici ◽  
Santina Di Bella ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Phylogenetic Analyses ◽  
Hepatitis E ◽  
Rt Pcr ◽  
High Seroprevalence ◽  
Genotype 3 ◽  
Sporadic Cases ◽  
Wild Boar Meat ◽  
Small Clusters ◽  
Frequent Exposure

In Europe, foodborne transmission has been clearly associated to sporadic cases and small clusters of hepatitis E in humans linked to the consumption of contaminated pig liver sausages, raw venison, or undercooked wild boar meat. In Europe, zoonotic HEV-genotype 3 strains are widespread in pig farms but little information is available on the prevalence of HEV positive pigs at slaughterhouse. In the present study, the prevalence of HEV-RNA positive pigs was assessed on 585 animals from 4 abattoirs located across Italy. Twenty-one pigs (3.6%) tested positive for HEV in either feces or liver by real-time RT-PCR. In these 21 pigs, eight diaphragm muscles resulted positive for HEV-RNA. Among animals collected in one abattoir, 4 out of 91 plasma tested positive for HEV-RNA. ELISA tests for the detection of total antibodies against HEV showed a high seroprevalence (76.8%), confirming the frequent exposure of pigs to the virus. The phylogenetic analyses conducted on sequences of both ORF1 and ORF2 fragments, shows the circulation of HEV-3c and of a novel unclassified subtype. This study provides information on HEV occurrence in pigs at the slaughterhouse, confirming that muscles are rarely contaminated by HEV-RNA compared to liver, which is the most frequently positive for HEV.

scholarly journals Hepatitis E Virus in Croatia in the “One-Health” Context

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 699
Author(s):  
Anna Mrzljak ◽  
Lorena Jemersic ◽  
Vladimir Savic ◽  
Ivan Balen ◽  
Maja Ilic ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Current Knowledge ◽  
Hepatitis E ◽  
Human Case ◽  
Interspecies Transmission ◽  
Genotype 3 ◽  
Chronic Patients ◽  
Indirect Contact ◽  
The One ◽  
Foodborne Infection

Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally. The first human case of autochthonous HEV infection in Croatia was reported in 2012, with the undefined zoonotic transmission of HEV genotype 3. This narrative review comprehensively addresses the current knowledge on the HEV epidemiology in humans and animals in Croatia. Published studies showed the presence of HEV antibodies in different population groups, such as chronic patients, healthcare professionals, voluntary blood donors and professionally exposed and pregnant women. The highest seroprevalence in humans was found in patients on hemodialysis in a study conducted in 2018 (27.9%). Apart from humans, different studies have confirmed the infection in pigs, wild boars and a mouse, indicating the interspecies transmission of HEV due to direct or indirect contact or as a foodborne infection. Continued periodical surveys in humans and animals are needed to identify the possible changes in the epidemiology of HEV infections.

scholarly journals Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rohan Sivapalan ◽  
Jinyan Liu ◽  
Krishnendu Chakraborty ◽  
Elisa Arthofer ◽  
Modassir Choudhry ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Therapy ◽  
Time Course ◽  
Mononuclear Cells ◽  
Adoptive Cell Therapy ◽  
Rapid Expansion ◽  
Effector Memory ◽  
Antigen Specificity ◽  
T Cell Therapy

AbstractThe a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a novel SARS-Cov-2-specific artificial antigen presenting cell (aAPC), coupled with a rapid expansion protocol (REP) as practiced in tumor infiltrating lymphocytes (TIL) therapy, we generate an immune catalytic quantity of Virus Induced Lymphocytes (VIL). Using T cell receptor (TCR)-specific aAPCs carrying co-stimulatory molecules and major histocompatibility complex (MHC) class-I immunodominant SARS-CoV-2 peptide-pentamer complexes, we expand virus-specific VIL derived from peripheral blood mononuclear cells (PBMC) of convalescent COVID-19 patients up to 1000-fold. This is achieved in a clinically relevant 7-day vein-to-vein time-course as a potential adoptive cell therapy (ACT) for COVID-19. We also evaluate this approach for other viral pathogens using Cytomegalovirus (CMV)-specific VIL from donors as a control. Rapidly expanded VIL are enriched in virus antigen-specificity and show an activated, polyfunctional cytokine profile and T effector memory phenotype which may contribute to a robust immune response. Virus-specific T cells can also be delivered allogeneically via MHC-typing and patient human leukocyte antigen (HLA)-matching to provide pragmatic treatment in a large-scale therapeutic setting. These data suggest that VIL may represent a novel therapeutic option that warrants further clinical investigation in the armamentarium against COVID-19 and other possible future pandemics.

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