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bioRxiv · 10.1101/2022.09.16.508338

Influenza virus membrane fusion is promoted by the endosome-resident phospholipid bis(monoacylglycero)phosphate

Mannsverk, S.·Villamil Giraldo, A. M.·Kasson, P. M.
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Abstract

The phospholipid bis(monoacylglycero)phosphate (BMP) is enriched in late endosomal and endo-lysosomal membranes and is believed to be involved in membrane deformation and generation of intralumenal vesicles within late endosomes. Previous studies have demonstrated that BMP promotes membrane fusion of several enveloped viruses, but a limited effect has been found on influenza virus. Here, we report the use of single-virus fusion assays to dissect BMPs effect on influenza virus fusion in greater depth. In agreement with prior reports, we found that hemifusion kinetics and efficiency were unaffected by the addition of 10-20 mol % BMP to the target membrane. However, using an assay for fusion pore formation and genome exposure, we found full fusion efficiency to be substantially enhanced by the addition of 10-20 mol % BMP to the target membrane, while the kinetics remained unaffected. By comparing BMP to other negatively charged phospholipids, we found the effect on fusion efficiency mainly attributable to headgroup charge, although we also hypothesize a role for BMPs unusual chemical structure. Our results suggest that BMP function as a permissive factor for a wider range of viruses than previously reported. We hypothesize that BMP may be a general co-factor for endosomal entry of enveloped viruses.

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Mannsverk, S., Villamil Giraldo, A. M., Kasson, P. M.. 2022-09-17. Influenza virus membrane fusion is promoted by the endosome-resident phospholipid bis(monoacylglycero)phosphate. https://doi.org/10.1101/2022.09.16.508338

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