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Midgut membrane protein BmSUH facilitates Bombyx mori nucleopolyhedrovirus oral infection
Yanting Liang1, Weifan Xu1, Yanyan Zhou1
1College of Animal Sciences, Zhejiang University, Hangzhou, China.
Abstract:
Baculoviruses are virulent pathogens that infect a wide range of insects. They initiate infections via specific interactions between the structural proteins on the envelopes of occlusion-derived virions (ODVs) and the midgut cell surface receptors in hosts. However, host factors that are hijacked by baculoviruses for efficient infection remain largely unknown. In this study, we identified a membrane-associated protein sucrose hydrolase (BmSUH) as an ODV binding factor during Bombyx mori nucleopolyhedrovirus (BmNPV) primary infection. BmSUH was specifically expressed in the midgut microvilli where the ODV-midgut fusion happened. Knockout of BmSUH by CRISPR/Cas9 resulted in a significantly higher survival rate after BmNPV orally infection. Liquid chromatography-tandem mass spectrometry analysis and co-immunoprecipitation analysis demonstrated that PIF protein complex required for ODV binding could interact with BmSUH. Furthermore, fluorescence dequenching assay showed that the amount of ODV binding and fusion to the midgut decreased in BmSUH mutants compared to wild-type silkworm, suggesting the role of BmSUH as an ODV binding factor that mediates the ODV entry process. Based on a multilevel survey, the data showed that BmSUH acted as a host factor that facilitates BmNPV oral infection. More generally, this study indicated that disrupting essential protein-protein interactions required for baculovirus efficient entry may be broadly applicable to against viral infection.
Insights
Scientists found that sucrose hydrolase (BmSUH) helps Bombyx mori nucleopolyhedrovirus (BmNPV) infect silkworms. Blocking BmSUH significantly increased silkworm survival, offering a new strategy against baculovirus infections.
Area of Science:
- Virology
- Insect Pathology
- Molecular Biology
Background:
- Baculoviruses are insect pathogens initiating infection through interactions between viral envelope proteins and host midgut receptors.
- Host factors mediating baculovirus entry remain largely unidentified, hindering the development of antiviral strategies.
Purpose of the Study:
- To identify host factors involved in Bombyx mori nucleopolyhedrovirus (BmNPV) oral infection.
- To elucidate the role of identified factors in the baculovirus entry process.
Main Methods:
- CRISPR/Cas9 gene editing to knockout BmSUH in Bombyx mori.
- Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation to analyze protein interactions.
- Fluorescence dequenching assays to quantify viral binding and fusion.
Main Results:
- Sucrose hydrolase (BmSUH) was identified as a key ODV binding factor, specifically expressed in midgut microvilli.
- BmSUH knockout significantly enhanced silkworm survival against BmNPV infection.
- BmSUH interacts with the PIF complex, facilitating ODV binding and midgut entry.
Conclusions:
- BmSUH acts as a crucial host factor that facilitates BmNPV oral infection by mediating viral entry.
- Targeting essential protein-protein interactions, like those involving BmSUH, presents a promising broad-spectrum strategy against baculovirus infections.
