posted on 2022-12-05, 12:03authored bySteinar Mannsverk, Ana M. Villamil Giraldo, Peter M. Kasson
The phospholipid bis(monoacylglycero)phosphate (BMP)
is enriched
in late endosomal and endolysosomal 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 BMP’s 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 BMP’s
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 cofactor for endosomal
entry of enveloped viruses.