Current liver research: Cell proliferation as Achilles heel for hepatitis B virus
11 May 2017
Infections caused by the hepatitis B virus (HBV) cannot be fully cured yet. This is because the virus places its genome in the nucleus of infected liver cells, where it is not accessible to existing therapies.
For the first time, SFB 841 scientists around Prof. Dr. Maura Dandri, head of project A5, have shown in a humanized mouse model that human host cells can get rid of the viral DNA by their natural cell division. Subsequently, they can be treated with standard medication in order to be protected from a reinfection.
“From related pathogens in animals it has long been known that infected liver cells lose large amounts of the viral DNA deposited in the cell nucleus when they divide,” explains Prof. Dandri, leader of the working group virus hepatitis in the I. Department of Medicine of the UKE. Now, for the first time, the scientists were able to detect this natural defense mechanism in a human HBV infection. “So far, there are no clinical therapy possibilities, which reach the virus DNA in the nucleus. It serves as a template for the reconstruction of new virus particles. But we were able to show that human liver cells also lose viral DNA on a large scale due to their cell division. This means that HBV has an Achilles heel”, Dandri states.
However, the study also shows why the host, despite cell division, only has small chances of completely freeing himself from the pathogen. “We have observed that infected cells showed a slower proliferation compared to non-infected cells. Single surviving infected cells can thus serve as a virus reservoir for new infections”, explains Dandri. Here, the treatment with anti-HBV drugs can be extremely advantageous: “By the simultaneous therapy with so-called entrance or polymerase inhibitors, a new infection could be efficiently blocked and the cells, which had freed themselves from the virus by cell division, could be protected”, Prof. Dandri concluded.
In the following video, Prof. Maura Dandri and Dr. Lena Allweiss, first author of the study, explain their new HBV research results (in German):
Die Achillesferse des Hepatitis B-VirusVideoarchivonline seit 19.04.2017
Allweiss L, Volz T, Giersch K, Kah J, Raffa G, Petersen J, Lohse AW, Beninati C, Pollicino T, Urban S, Lütgehetmann M, Dandri M
Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo.
Gut. 2017 Apr 20. pii: gutjnl-2016-312162. doi: 10.1136/gutjnl-2016-312162..