[转移贴] 胆固醇对于嗜肝DNA病毒致病性影响

cao1976

原贴由bigben发表于 2009-4-10 23:09

Title: Duck hepatitis B virus requires cholesterol for endosomal escape during virus entry.
Author: Funk, A.; Mhamdi, M.; Hohenberg, H. (...)
Source: J Virol, 2008, 82(21): 10532-10542
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.

Title: Hepatitis B virus infection is dependent on cholesterol in the viral envelope.
Author: Bremer, C. M.; Bung, C.; Kott, N. (...)
Source: Cell Microbiol, 2009, 11(2): 249-260
Abstract:
  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 (MbetaCD) 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.