Projects Translational Virology

Identification of neutralizing antibodies against HEV

In close collaboration with the team of Prof. T. Krey (University of Lübeck, Institute of Biochemistry, Germany) we investigate to what extent human monoclonal antibodies represent a therapeutic option against the virus. In particular, the SARS-Cov-2 pandemic has shown that this strategy can be safe and effective. We focus on antibodies that are present in the blood of individuals who have overcome an HEV infection. The goal is to identify and synthesize these antibodies and later use them as therapy for infected patients. The evaluation of the identified antibodies plays an important role with regard to their ability to prevent the virus from entering the cell (neutralization). Additionally, we would like to identify antibodies that bind and neutralize all subtypes of the virus (so-called genotypes).

Extrahepatic replication of the hepatitis E virus

Infection with HEV is associated with extrahepatic manifestations such as neurologic complaints or renal function deterioration in some individuals. In addition, infections with genotypes 1 and 2 (prevalent primarily in Africa) can cause severe courses inpregnant women. So far, it is unclear whether these extrahepatic manifestations are caused by direct infection of the respective organ system (neurons, placental cells, renal cells) or are indirect. We are therefore using our cell culture generated virus to test for possible infection of different human cells derived from different organ systems. These studies will reveal whether direct infection of these organs with the virus is possible and have implications for monitoring HEV patients in the context of infection. 

 

Inactivation of Hepatitis E

The efficient cell culture system for HEV established at TWINCORE enables the analysis of different inactivation methods of the virus. We are currently using this to analyze the inactivation of the virus by commercially available hand disinfectants. The knowledge gained from this will significantly influence the hygienic measures that are taken in the event of an infection.

 

 

Publications

Behrendt P, Bremer B, Todt D, Brown RJ, Heim A, Manns MP, Steinmann E, Wedemeyer H: Hepatitis E Virus (HEV) ORF2 Antigen Levels Differentiate Between Acute and Chronic HEV Infection. J Infect Dis 2016, 214(3):361-368.

Behrendt P, Bremer B, Todt D, Steinmann E, Manns MP, Cornberg M, Wedemeyer H, Maasoumy B: Significant compartment-specific impact of different RNA extraction methods and PCR assays on the sensitivity of hepatitis E virus detection. Liver Int 2021, 41(8):1815-1823.

Schlevogt B, Kinast V, Reusch J, Kerkhoff A, Praditya D, Todt D, Schmidt HH, Steinmann E, Behrendt P: Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment. Pathogens 2019, 8(3).

Todt D, Friesland M, Moeller N, Praditya D, Kinast V, Bruggemann Y, Knegendorf L, Burkard T, Steinmann J, Burm R et al: Robust hepatitis E virus infection and transcriptional response in human hepatocytes. Proc Natl Acad Sci U S A 2020, 117(3):1731-1741.