Duck Hepatitis B Virus Requires Cholesterol for Endosomal Escape during Virus Entry

Abstract

The identity and functionality of biological membranes are determined by cooperative interaction between their lipid and protein constituents. Cholesterol is an important structural lipid that modulates fluidity of biological membranes favoring the formation of detergent-resistant microdomains. In the present study, we evaluated the functional role of cholesterol and lipid rafts for entry of hepatitis B viruses into hepatocytes. We show that the duck hepatitis B virus (DHBV) attaches predominantly to detergent-soluble domains on the plasma membrane. Cholesterol depletion from host membranes and thus disruption of rafts does not affect DHBV infection. In contrast, depletion of cholesterol from the envelope of both DHBV and human HBV strongly reduces virus infectivity. Cholesterol depletion increases the density of viral particles and leads to changes in the ultrastructural appearance of the virus envelope. However, the dual topology of the viral envelope protein L is not significantly impaired. Infectivity and density of viral particles are partially restored upon cholesterol replenishment. Binding and entry of cholesterol-deficient DHBV into hepatocytes are not significantly impaired, in contrast to their release from endosomes. We therefore conclude that viral but not host cholesterol is required for endosomal escape of DHBV.

Hepatitis B Virus Requires Intact Caveolin-1 Function for Productive Infection in HepaRG Cells

“…Recently published data demonstrated that DHBV preferentially binds to detergent-soluble domains of the duck hepatocyte plasma membrane (13). Combined with the failure of M␤CD treatment to inhibit DHBV infection, the observation suggests that caveolae may not be involved in DHBV entry.…”

“…Using chemical compounds that either extract or interfere with the biosynthesis of this lipid, it was shown that cholesterol depletion from host membranes does not affect the internalization of duck HBV (DHBV), the avian member of the hepadnaviruses. In contrast, cholesterol extraction from the envelopes of both DHBV and human HBV strongly reduces virus infectivity, possibly interfering with its release from endosomes (6,13).…”

Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

“…Data shown are representatives of images and the mean ± SD of the relative levels of intermediates in the cells treated with each compound from three independent experiments. There were similar levels of integrated HBV DNA among different groups of cells (data not shown) DHBV has high similarity in biological and structural properties to human HBV (Funk et al, 2008;Girard et al, 2007;Schultz et al, 2004). We found that oral treatment of naturally DHBV-infected ducks with different concentrations of each compound significantly reduced the concentrations of serum DHBV DNA and decreased inflammation in the livers.…”

Hepatitis B virus infection: An insight into infection outcomes and recent treatment options

“…Surface protein synthesis occurs in the ER where the cytoplasmically preformed nucleocapsids are enveloped with these surface proteins and then released via the constitutional secretion pathway [25]. The envelopment results from highly co-ordinated biological interactions between the nucleocapsids and the cytoplasmically exposed pre-S region of the L protein.…”