Single-Virus Lipid-Mixing Study of Sendai Virus Provides Insight into Fusion Mechanism

TL;DR

This study uses single-virus experiments to understand how Sendai virus fuses with cell membranes, revealing it is slow and inefficient compared to other viruses.

Contribution

The first single-virus lipid-mixing study of a paramyxovirus, providing new insights into its fusion mechanism.

Findings

Fusion wait times of Sendai virus follow an exponential distribution, indicating a single rate-limiting step.

Fusion is slow (tens of minutes) and inefficient, with only a small fraction of virions fusing.

Trypsin treatment and receptor variation affect fusion efficiency but not the wait time distribution.

Abstract

Single-virus studies have proven useful to interrogate
the entry
mechanism for several viral families. Here, we employ a fluorescence
microscopy-based single-virus assay to study the fusion (lipid mixing)
of Sendai virus to model membranes, the first for any paramyxovirus
to our knowledge. We find that fusion wait times following binding
are exponentially distributed, suggesting a single rate-limiting step.
Compared to previously studied viruses, fusion is relatively slow
(tens of minutes) and inefficient (only a small fraction of virions
undergo fusion). Trypsin treatment of the virus or different viral
receptors in the target alter the efficiency, although the wait time
distribution remains unchanged in both cases. This provides constraints
on the fusion mechanism and the identity of the rate-limiting step.
Together, our data paint a picture of Sendai virus as a comparatively
inefficient and slow fusion “machine” and set the stage
for the investigation of other paramyxoviruses.

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