Inhibition of influenza virus fusion by polyanionic proteinsSchoen, P. J., Corver, J., Meijer, D. K. F., Wilschut, J. & Swart, P. J., 4-Apr-1997, In : Biochemical Pharmacology. 53, 7, p. 995-1003 9 p.
Research output: Contribution to journal › Article › Academic › peer-review
Anionic charge-modified human serum albumin (HSA) has previously been shown to exert potent in vitro activity against human immunodeficiency virus type 1 (HIV-1). In these studies, introduction of the additional negative charges was performed by derivatizing the epsilon-amino groups of lysine residues with succinic (Suc-HSA) or cis-aconitic anhydride (Aco-HSA), by which primary amino groups are replaced with carboxylic acids. The anti-HIV-1 activity was related to inhibition of gp41-mediated membrane fusion. Here, we investigated the activity of aconitylated and succinylated proteins on influenza Virus membrane fusion, which is mediated by the viral membrane glycoprotein hemagglutinin (HA). Aco-HSA and Suc-HSA markedly inhibited the rates and extents of fusion of fluorescently labeled virosomes bearing influenza HA, with target membranes derived from erythrocytes. The inhibitory activity was dependent on the overall negative-charge density; HSA modified with 36 or less extra negative charges failed to inhibit fusion. The inhibition of fusion showed a certain degree of specificity for the protein carrying the negative charges: polyanionic HSA and beta-lactoglobulin A derivatives had fusion-inhibitory activity, whereas succinylated BSA, lactalbumin, lactoferrin, lysozyme, and transferrin were inactive. Aco(60)-HSA and Aco-beta-lactoglobulin A inhibited influenza virus membrane fusion in a concentration-dependent manner, IC50 values being about 4 and 10 mu g/mL, respectively. HA-mediated membrane fusion is pH dependent. Aco(60)-HSA did not induce a shift in the pH threshold or in the pH optimum. Fusion with liposomes of another low pH-dependent virus, Semliki Forest virus, was not specifically affected by any of the compounds reported here. In view of some structural and functional similarities between influenza HA and the HIV-1 gp120/gp41 complex, it is tempting to postulate that the current results might have some implications for the anti-HIV-1 mechanism of polyanionic proteins. (C) 1997 Elsevier Science Inc.
|Number of pages||9|
|Publication status||Published - 4-Apr-1997|
- influenza virus, hemagglutinin, antiviral agents, serum albumin, membrane fusion, polyanions, HUMAN-IMMUNODEFICIENCY-VIRUS, SEMLIKI-FOREST-VIRUS, HEMAGGLUTININ MEMBRANE GLYCOPROTEIN, HUMAN SERUM ALBUMINS, DEXTRAN SULFATE, IN-VITRO, HEPTAD REPEAT, REPLICATION, KINETICS, POTENT