Journal
JOURNAL OF IMMUNOLOGY
Volume 207, Issue 3, Pages 888-901Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2001056
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Funding
- National Natural Science Foundation of China [U1602226, 81672040]
- Yunling Scholar Program
- Applied Basic Research Joint Special Fund Project of Yunnan Provincial Science and Technology Department-Kunming Medical University [202001AY070001-002]
- Yunnan Top-notch Young Talents Program
- Yunnan Province Thousand Talent Award
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The study demonstrates that a toxin aerolysin-like protein and trefoil factor complex (βγ-CAT) from the frog Bombina maxima can directly block enveloped virus invasion by interfering with cytoplasmic entry, particularly inhibiting HSV-1 infection. βγ-CAT induces pore formation on the HSV-1 envelope, hindering viral entry into host cells and providing a potential antiviral strategy.
Because most of animal viruses are enveloped, cytoplasmic entry of these viruses via fusion with cellular membrane initiates their invasion. However, the strategies in which host cells counteract cytoplasmic entry of such viruses are incompletely understood. Pore-forming toxin aerolysin-like proteins (ALPs) exist throughout the animal kingdom, but their functions are mostly unknown. In this study, we report that By-crystallin fused aerolysin-like protein and trefoil factor complex (beta gamma-CAT), an ALP and trefoil factor complex from the frog Bombina maxima, directly blocks enveloped virus invasion by interfering with cytoplasmic entry. beta gamma-CAT targeted acidic glycosphingolipids on the HSV type 1 (HSV-1) envelope to induce pore formation, as indicated by the oligomer formation of protein and potassium and calcium ion efflux. Meanwhile, beta gamma-CAT formed ring-like oligomers of similar to 10 nm in diameter on the liposomes and induced dye release from liposomes that mimic viral envelope. Unexpectedly, transmission electron microscopy analysis showed that the beta gamma-CAT-treated HSV-1 was visibly as intact as the vehicle-treated HSV-1, indicating that beta gamma-CAT did not lyse the viral envelope. However, the cytoplasmic entry of the beta gamma-CAT-treated HSV-1 into HeLa cells was totally hindered. In vivo, topical application of beta gamma-CAT attenuated the HSV-1 corneal infection in mice. Collectively, these results uncovered that beta gamma-CAT possesses the capacity to counteract enveloped virus invasion with its featured antiviral-acting manner. Our findings will also largely help to illustrate the putative antiviral activity of animal ALPs.
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