| An aerolysin-like pore-forming protein complex targets viral envelope to inactivate herpes simplex virus type 1 |
| 2021-12-03
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An aerolysin-like pore-forming protein complex targets viral envelope to inactivate herpes simplex virus type 1. J Immunol, 2021Title:An aerolysin-like pore-forming protein complex targets viral envelope to inactivate herpes simplex virus type 1 Author:Liu L, Deng CJ, Duan YL, Ye CJ, Gong DH, Guo XL, Lee WH, Zhou J, Li SA, Zhang Y. Publication Name: J Immunol Pub Year: 2021 Doi: 10.4049/jimmunol.2001056 IF: 5.442 Abstract: 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 betagamma-crystallin fused aerolysin-like protein and trefoil factor complex (betagamma-CAT), an ALP and trefoil factor complex from the frog Bombina maxima, directly blocks enveloped virus invasion by interfering with cytoplasmic entry. betagamma-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, betagamma-CAT formed ring-like oligomers of 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 betagamma-CAT-treated HSV-1 was visibly as intact as the vehicle-treated HSV-1, indicating that betagamma-CAT did not lyse the viral envelope. However, the cytoplasmic entry of the betagamma-CAT-treated HSV-1 into HeLa cells was totally hindered. In vivo, topical application of betagamma-CAT attenuated the HSV-1 corneal infection in mice. Collectively, these results uncovered that betagamma-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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