Midgut membrane protein BmSUH facilitates Bombyx mori nucleopolyhedrovirus oral infection

PLoS Pathog. 2022 Nov 16;18(11):e1010938. doi: 10.1371/journal.ppat.1010938. eCollection 2022 Nov.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae
  • Bombyx*
  • Digestive System
  • Membrane Proteins / metabolism
  • Nucleopolyhedroviruses* / metabolism

Substances

  • Membrane Proteins

Supplementary concepts

  • Bombyx mori nucleopolyhedrovirus

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant no. 32170483 and 31970460 to H.B.W), Natural Science Foundation of Zhejiang Province (grant no. LR22C040001 to H.B.W), Zhejiang Provincial Science and Technology Plans (grant no. 2021C02072-6 to H.B.W), and Zhejiang Provincial Key Laboratory Construction Plans (grant no. 2020E10025 to H.B.W). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.