Open AccessHepatitis B virus infection is dependent on cholesterol in the viral envelope
Author(s) -
Bremer Corinna M.,
Bung Christiane,
Kott Nicole,
Hardt Martin,
Glebe Dieter
Publication year - 2009
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2008.01250.x
Subject(s) - infectivity , cholesterol , biology , viral entry , viral envelope , virology , hepatitis b virus , filipin , lipid raft , virus , hepatocyte , in vitro , viral replication , biochemistry
Summary The viral and cellular determinants leading to binding and entry of hepatitis B virus (HBV) are still not fully understood. We found that HBV infection of primary hepatocyte cultures is dependent on the presence of cholesterol in the viral envelope. Extraction of cholesterol from HBV purified from plasma of HBV‐infected patients with methyl‐beta‐cyclodextrin (MβCD) leads to a strongly reduced level of infection. The cholesterol‐depleted virions showed higher buoyant density (1.23 versus 1.17 g ml −1 ), a smaller diameter (39 versus 48 nm), but maintained particle integrity, antigenicity and ability to bind to hepatocytes. Although addition of exogenous cholesterol and cholesterol analogues restored the physical appearance of cholesterol‐depleted virions, infectivity was only regained by cholesterol add‐back. Infectivity of HBV produced from cell culture in the presence of inhibitors of cholesterol‐synthesis is severely impaired. Interestingly, cholesterol extraction from cellular membranes, incubation with filipin and the protein tyrosine kinase inhibitor genistein showed no effect on HBV infection, excluding a role of lipid rafts for the infection process of HBV. In summary, presence of cholesterol within the viral envelope is not important for viral binding, but indispensable for the entry process of HBV and might be important for a later step in viral uptake, e.g. fusion in a yet unknown compartment.