Collective Fusion Activity Determines Neurotropism of an En Bloc Transmitted Enveloped Virus

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Jan 27

PMID 36706187

Authors

Yuta Shirogane

Hidetaka Harada

Yuichi Hirai

Ryuichi Takemoto

Tateki Suzuki

Takao Hashiguchi

Yusuke Yanagi

Affiliations

Soon will be listed here.

Abstract

Measles virus (MeV), which is usually non-neurotropic, sometimes persists in the brain and causes subacute sclerosing panencephalitis (SSPE) several years after acute infection, serving as a model for persistent viral infections. The persisting MeVs have hyperfusogenic mutant fusion (F) proteins that likely enable cell-cell fusion at synapses and "en bloc transmission" between neurons. We here show that during persistence, F protein fusogenicity is generally enhanced by cumulative mutations, yet mutations paradoxically reducing the fusogenicity may be selected alongside the wild-type (non-neurotropic) MeV genome. A mutant F protein having SSPE-derived substitutions exhibits lower fusogenicity than the hyperfusogenic F protein containing some of those substitutions, but by the wild-type F protein coexpression, the fusogenicity of the former F protein is enhanced, while that of the latter is nearly abolished. These findings advance the understanding of the long-term process of MeV neuropathogenicity and provide critical insight into the genotype-phenotype relationships of en bloc transmitted viruses.

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