Projects Virus Transmission

Intervention strategies against HEV

Co-infection with HCV and HEV. HCV infected cells are pigmented red, HEV infected green.

Hepatitis E virus (HEV) can take chronic infections in immunocompromised patients leading to liver cirrhosis and liver failure. Ribavirin is currently the only treatment option for many patients, but treatment failure can occur, which has been associated with a mutation in the HEV polymerase. We aim to investigate HEV polymerase evolution prior to and during ribavirin therapy in patients with chronic hepatitis to understand the mode of action of the drug in vivo (Todt et al. Gut 2016). Furthermore, we could demonstrate for the first time in tissue culture that HEV replication is not restricted to the liver and can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurological disorders during HEV infection (Drave et al. JVH 2016). As another goal, we plan together with partners from the Helmholtz Center for Infection Research to screen natural compounds against HEV replication to discover novel compounds for the treatment of HEV infections.


Transmission and prevention measures of HCV

The aim is to understand and explore ways of HCV transmission in the environment especially in healthcare settings and among injection drug users. In the past, we evaluated the environmental stability of HCV and its susceptibility to chemical biocides (Ciesek et al. JID 2010) and against novel disinfectant formulations proposed by the WHO (Steinmann et al. AJIC 2010, Steinmann et al. ARIC et al. 2013). Furthermore, we could show that HCV-contaminated medication like propofol or fentanyl can influence virus stability (Steinmann et al. CID 2011, Behrendt et al. AJIC 2013). More recently, we also studied cross-transmission among PWID’s by contamination of drug preparation equipment and survival of dried HCV on inanimate surfaces (Doerrbecker et al. JID 2011, Doerrbecker et al. JID 2013). Furthermore, we evaluated the influence of heroin of HCV and HIV-1 infectivity in a drug transmission assay and characterized the use of microwaves as prevention strategy for these blood-borne viruses (Siddharta et al. Sci Rep 2016).


Intervention strategies against HEV

Knegendorf L, Drave SA, Dao Thi VL, Debing Y, Brown RJP, Vondran FWR, Resner K, Friesland M, Khera T, Engelmann M, Bremer B, Wedemeyer H, Behrendt P, Neyts J, Pietschmann T, Todt D, Steinmann E. Hepatitis E virus replication and interferon responses in human placental cells. Hepatol Commun. 2018 Jan 8;2(2):173-187

Weller R, Todt D, Engelmann M, Friesland M, Wedemeyer H, Pietschmann T, Steinmann E. Apolipoprotein E polymorphisms and their protective effect on hepatitis E virus replication. Hepatology. 2016 Dec;64(6):2274-2276.

Todt D, Walter S, Brown RJ, Steinmann E. Mutagenic effects of ribavirin on hepatitis E virus-viral extinction versus selection of fitness-enhancing mutations. Viruses 2016 Oct 13;8(10).

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 Aug 1;214(3):361-8.

Todt D, Gisa A, Radonic A, Nitsche A, Behrendt P, Suneetha PV, Pischke S, Bremer B, Brown RJ, Manns MP, Cornberg M, Bock CT, Steinmann E*, Wedemeyer H*. In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. Gut. 2016 Oct;65(10):1733-43.

Drave SA, Debing Y, Walter S, Todt D, Engelmann M, Friesland M, Wedemeyer H, Neyts J, Behrendt P, Steinmann E. Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells. J Viral Hepat. 2016 Jul;23(7):512-21.

Todt D, François C, Anggakusuma, Behrendt P, Engelmann M, Knegendorf L, Vieyres G, Wedemeyer H, Hartmann R, Pietschmann T, Duverlie G, Steinmann E. Antiviral Activities of Different Interferon Types and Subtypes against Hepatitis E Virus Replication. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2132-9.

Behrendt P, Steinmann E, Manns MP, Wedemeyer H. The impact of hepatitis E in the liver transplant setting. J Hepatol. 2014 Dec;61(6):1418-29.

Transmission and prevention measures of HCV

Ciesek S, Friesland M, Steinmann J, Becker B, Wedemeyer H, Manns MP, Steinmann J, Pietschmann T, Steinmann E (2010) How stable is the hepatitis C virus (HCV)? Environmental stability of HCV and its susceptibility to chemical biocides. J Infect Dis 201(12): 1859-1866.

Steinmann J, Becker B, Bischoff B, Paulmann D, Friesland M, Pietschmann T, Steinmann J, Steinmann E (2010) Virucidal activity of 2 alcohol-based formulations proposed as hand rubs by the World Health Organization. Am J Infect Control 38(1): 66-68.

Steinmann J, Becker B, Bischoff B, Magulski T, Steinmann J, Steinmann E (2013) Virucidal activity of Formulation I of the World Health Organization's alcohol-based handrubs: impact of changes in key ingredient levels and test parameters. Antimicrob Resist Infect Control 2(1): 34.

Steinmann E, Ciesek S, Friesland M, Erichsen TJ, Pietschmann T (2011) Prolonged survival of hepatitis C virus in the anesthetic propofol. Clin Infect Dis 53(9): 963-964.

Behrendt P, Doerrbecker J, Riebesehl N, Wilhelm C, Ciesek S, Erichsen TJ, Steinmann J, Ott M, Manns MP, Pietschmann T, Steinmann E (2013) Stability and transmission of hepatitis C virus in different anesthetic agents. Am J Infect Control 41(10): 942-943.

Doerrbecker J, Friesland M, Ciesek S, Erichsen TJ, Mateu-Gelabert P, Steinmann J, Steinmann J, Pietschmann T, Steinmann E (2011) Inactivation and survival of hepatitis C virus on inanimate surfaces. J Infect Dis 204(12): 1830-1838.

Doerrbecker J, Behrendt P, Mateu-Gelabert P, Ciesek S, Riebesehl N, Wilhelm C, Steinmann J, Pietschmann T, Steinmann E (2013) Transmission of hepatitis C virus among people who inject drugs: viral stability and association with drug preparation equipment. J Infect Dis 207(2): 281-287.

Siddharta A, Pfaender S, Malassa A, Doerrbecker J, Anggakusuma, Engelmann M, Nugraha B, Steinmann J, Todt D, Vondran FW, Mateu-Gelabert P, Goffinet C, Steinmann E (2016) Inactivation of HCV and HIV by microwave: a novel approach for prevention of virus transmission among people who inject drugs. Sci Rep 6: 36619.