Fusion and infection of influenza and Sendai viruses as modulated by dextran sulfate: a comparative study.
We have directly compared the effect of two types of dextran sulfate with distinct molecular weights (500 kDa and 5 kDa) on the fusion activity and infectivity of both Sendai and influenza viruses, two lipid-enveloped viruses that differ in their routes of entry into target cells. To correlate membrane merging and infectivity MDCK cells were used as targets for the viruses in both approaches. In either case pronounced inhibition of virus-cell interactions by dextran sulfate was only observed at low pH, even though Sendai virus fuses maximally at pH 7.4. Although membrane merging could not be fully abolished, the inhibitory effect was always greater when the higher molecular weight dextran sulfate was used. The presence of this residual fusion activity, that could not be reduced even with high concentrations of agent, suggests that a limited number of binding sites for dextran sulfate may exist on the viral envelopes. The compounds also inhibited fusion of bound virions, and all results could be reproduced using erythrocyte ghosts as target membranes in the fusion assay, instead of MDCK cells. In agreement with these observations only the infectivity of influenza virus (which requires a low pH-dependent step to enter target cells) was affected by dextran sulfate, again the higher molecular weight compound showing a more pronounced inhibitory effect.
Ramalho-Santos
J
J
Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, Portugal. jramalho@ci.uc.pt
de Lima
M C
MC
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007251:Influenza, Human / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008561:Membrane Fusion / Q000187:drug effects* / Q000502:physiology; D008970:Molecular Weight; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D010253:Respirovirus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D029082:Sendai virus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D014760:Viral Fusion Proteins / Q000187:drug effects* / Q000378:metabolism
D014760:Viral Fusion Proteins; D016264:Dextran Sulfate