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Fusion of enveloped viruses with cells and liposomes

Activity and inactivation

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Abstract

The fusion of viruses with cells and liposomes is reviewed with focus on the analysis of the final extents and kinetics of fusion.Influenza virus andSendai virus exhibit 100% of fusion capacity with cells at pH 5 and pH 7.5, respectively. On the other hand, there may be in certain cases, a limit on the number of virions that can fuse with a single cell, that is significantly below the limit on binding. It still remains to be resolved whether this limit reflects a limited number of possible fusion sites, or a saturation limit on the amount of viral glycoproteins that can be incorporated in the cellular membrane, like the case of virus fusion with pure phospholipid vesicles, in which the fusion products were shown to consist of a single virus and several liposomes. Both viruses demonstrate incomplete fusion activity towards liposomes of a variety of compositions. In the case ofSendai virus, fusion inactive virions bind essentially irreversibly to liposomes. Yet, preliminary results revealed that such bound, unfused virions can be released by sucrose gradient centrifugation. The separated unfused virions subsequently fuse when incubated with a “fresh” batch of liposomes. We conclude, therefore, that the fraction of initially bound unfused virions does not consist of dective particles, but rather of particles bound to liposomes via “inactive” sites.

Details of the low pH inactivation of fusion capacity ofinfluenza virus towards cells and liposomes are presented. This inactivation is caused by protonation and exposure of the hydrophobic segment of HA2, and affects primarily the fusion rate constants. Some degree of inactivation also occurs when virions are bound to cellular membranes.

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Abbreviations

CL:

cardiolipin

Chol:

cholesterol

PG:

phosphatidylglycerol

PE:

phosphatidylethanolamine

PC:

phosphatidylcholine

PS:

phosphatidylserine

DOPC:

dioleoylphosphatidylcholine

LUV:

large unilamellar vesicles

R18 :

octadecylrhodamine B chloride

PEG:

poly(ethylene glycol)

MW:

8000

HIV:

human immunodeficiency virus

SFV:

Semliki forest virus

VSV:

vesicular stomatitis virus

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Nir, S., Düzgünes, N., Pedroso De Lima, M.C. et al. Fusion of enveloped viruses with cells and liposomes. Cell Biophysics 17, 181–201 (1990). https://doi.org/10.1007/BF02990496

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