A broad antiviral neutral glycolipid, fattiviracin FV-8, is a membrane fluidity modulator.
To screen for an effective antiviral compound which acts as a membrane fluidity modulator, dichotomous effects on human immunodeficiency virus type 1 (HIV-1) infection due to different treatments of several glycolipids and lipids were examined. Continuous treatment of infected cells with 40 microg ml(-1) fattiviracin FV-8, a neutral glycolipid isolated from Streptomycetes, inhibited HIV-1 infection by 96%, whereas pretreatment with 400 microg ml(-1) enhanced infectivity 4.7-fold. The glycolipid showed similar effects as glycyrrhizin; it inhibited infection by broad enveloped viruses, blocked cell-cell fusion, reduced the infectivity of treated virions and enhanced susceptibility to viral infection and cell-cell fusion of cells pretreated with high doses of the compound. Suppression and enhancement was correlated with decreased and increased fluidity of plasma membrane of the fattiviracin FV-8-treated cells. Restricted movement of membrane molecules might impede the formation of a wide fusion pore, and therefore be critical to the entry of viruses. Thus, this can be applied as a new strategy to inhibit viral infections.
Harada
Shinji
S
Department of Medical Virology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. biodef@gpo.kumamoto-u.ac.jp
Yokomizo
Kazumi
K
Monde
Kazuaki
K
Maeda
Yosuke
Y
Yusa
Keisuke
K
D000818:Animals; D019556:COS Cells; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical; D006017:Glycolipids / Q000378:metabolism / Q000494:pharmacology*; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects*
D006017:Glycolipids; D023581:HIV Fusion Inhibitors; C437408:fattiviracin FV-8; D019695:Glycyrrhizic Acid