The broad anti-viral agent glycyrrhizin directly modulates the fluidity of plasma membrane and HIV-1 envelope.
Cell entry of enveloped viruses requires a wide-fusion-pore mechanism, involving clustering of fusion-activated proteins and fluidization of the plasma membrane and viral envelope. In the present study, GL (glycyrrhizin) is reported to lower membrane fluidity, thus suppressing infection by HIV, influenza A virus and vesicular stomatitis virus, but not by poliovirus. GL-treated HIV-1 particles showed reduced infectivity. GL also inhibited cell-to-cell fusion induced by HIV-1 and HTLV-I (human T-cell leukaemia virus type I). However, when cells treated with 1 mg/ml GL were placed in GL-free medium, they showed increased susceptibility to HIV-1 infection and HTLV-I fusion due to enhancement of membrane fluidity. The membrane dependence of GL and GL removal experiments suggest that GL does affect the cell entry of viruses. HIVs with more gp120 were less dependent on temperature and less sensitive to GL treatment than those with less gp120, indicating that the existence of more gp120 molecules resulted in a higher probability of forming a cluster of fusion-activated proteins.
Harada
Shinji
S
Department of Medical Virology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. biodef@gpo.kumamoto-u.ac.jp
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008560:Membrane Fluidity / Q000187:drug effects*; D015394:Molecular Structure; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D014759:Viral Envelope Proteins; D019695:Glycyrrhizic Acid