The role of the endoplasmic reticulum-associated degradation in establishment of persistent Hepatitis B Virus infection

The role of the endoplasmic reticulum-associated degradation in establishment of persistent Hepatitis B Virus infection 2013-2016
Acronym: HBVERAD
Budget: 174.400 Euro
Project director: Catalin Lazar

The objectives of this project aim to identify as many as possible cell proteins with a role in processing HBV envelpe proteins and to make a correlation between the HBV cccDNA which is the replicative form of the virus and the expression level of cellular proteins involved in the debradation of the HBV envelope proteins. The results will be confirmed in vivo using human hepatocytes explanted from the patiens chronically infected with HBV.

Hepatitis B Virus (HBV) is an important human pathogen which can cause life-threatening liver infection. Chronic HBV infection is correlated with a strongly increased risk for the development of liver cirrhosis and hepatocellular carcinoma (HCC). The viral DNA genome is packaged inside the nucleocapsid, surrounded by a lipid bilayer which contains three transmembrane proteins. These proteins, designated large (L), middle (M) and small (S) are synthesized in the endoplasmic reticulum (ER) at a high level to meet the needs of the virus to secrete both viral and subviral particles. The accumulation of unfolded or aggregated proteins in the cell can trigger ER stress. Our previously results showed that EDEMs (ER degradation-enhancing alpha-mannosidase-like) proteins were significantly up-regulated in HBV replicating cells. Co-expression of the wild-type HBV envelope proteins with EDEM1 resulted in their massive degradation, a process reversed by EDEM1 silencing. Surprisingly, the autophagy/lysosomes, rather than the proteasomes were involved in disposal of the HBV envelope proteins. And most importantly, inhibition of the endogenous EDEM1 expression significantly increased secretion of both, enveloped virus and subviral particles.

In this context, this project proposal intends to pursue these important findings and gain more insights into the role of the ERAD components in the HBV life-cycle and the establishment of persistent infection, both in vitro and in vivo.

Catalin Lazar, PhD
Catalin Lazar, PhD

Scientific Researcher II

Catalin Lazar is a researcher in the Institute of Biochemistry of the Romanian Academy. Catalin is currently working in Viral Glycoproteins in the Viral Glycoproteins.