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Molecular mechanisms of hepatitis B virus egress

Molecular mechanisms of hepatitis B virus egress 2018-2020
Acronym: HBVEGRESS
Project director: Catalin Lazar
External website: full link

Hepatitis B virus (HBV) chronic infection frequently leads to liver disease such as cirrhosis and hepatocellular carcinoma (HCC). As a result of severe liver pathogenesis, more than 500,000 infected patients die yearly. HBV is a small, enveloped DNA virus belonging to the Hepadnaviridae family. The viral genome coding for capsid (C), polymerase (P), viral X protein (HBx) and three envelope proteins (S, M and L) is only 3.1 Kbp wide.
 To accomplish distinct steps in a typical virus life cycle - entry, replication, assembly, and egress - viruses are able to manipulate cellular mechanisms for their own benefit. The autophagy, a lysosomal-dependent degradation pathway, has very important roles in HBV life cycle. HBV induces non-degradative autophagy, which in turn promotes viral replication. However, several research groups have claimed that autophagy exerts a suppressive effect in HBV-related HCC tumorigenesis, indicating the complex relationship between the pathogen and this cellular pathway.
 The mechanism by which the HBV is assembled and released from infected hepatocytes is poorly understood. The current grant proposal is focused around the hypothesis that secretory autophagy, a newly described unconventional secretion pathway, regulates HBV exit from infected cells. To investigate this possibility, we will first modulate the expression level of several key proteins involved in secretory autophagy in (i) HBV-replicating hepatoma cells, (ii) HEK293T cells overexpressing S, M or L viral glycoproteins, or in (iii) differentiated HepaRG cells supporting HBV infection. The influence of autophagy-based unconventional secretion will be further determined by monitoring different aspects of the HBV life cycle. Provided our hypothesis is confirmed, we will not only shed light on a very important and mostly obscure step of the HBV life cycle – the viral egress – but also, the secretion regulatory proteins could be used as possible targets against viral spread 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.

Mihaela-Olivia Dobrica, PhD
Mihaela-Olivia Dobrica, PhD

Research Assistant

Mihaela-Olivia Dobrica is a researcher in the Institute of Biochemistry of the Romanian Academy. Mihaela-Olivia is currently working in Viral Glycoproteins in the Viral Glycoproteins.