January 30, 2023
Professor Yusuke Yanagi of the National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University, in collaboration with Assistant Professor Yuta Shirogane and Hidetaka Harada of Kyushu University, and Professor Takao Hashiguchi and Assistant Professor Tateki Suzuki of Kyoto University, analyzed the fusion (F) gene of the measles virus derived from patients with subacute sclerosing panencephalitis (SSPE). As a result, they found that the interaction between mutant and wild-type F proteins is an essential factor that determines the neuroproliferative potential of the virus, revealing a new mechanism of virus evolution.
The findings are expected to be helpful for the development of SSPE therapeutics targeting F protein interactions and reveal the evolutionary mechanism of viruses that use membrane fusion proteins for cell entry (e.g., coronaviruses and herpesviruses).
The research results were published in the U.S. online scientific journal Science Advances on Saturday, January 28, 2023.
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.
Title：Collective fusion activity determines neurotropism of an en bloc transmitted enveloped virus
Author information：Yuta Shirogane, Hidetaka Harada, Yuichi Hirai, Ryuichi Takemoto, Tateki Suzuki, Takao Hashiguchi, and Yusuke Yanagi
This release is also available in Japanese.