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TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection
Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, the leading cause of viral-induced encephalitis. Several host molecules have been identified as the JEV attachment factor; however, the molecules involved in JEV entry remain poorly understood. In the present study, we demonstrate tha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265761/ https://www.ncbi.nlm.nih.gov/pubmed/30441759 http://dx.doi.org/10.3390/v10110630 |
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author | Niu, Jichen Jiang, Ya Xu, Hao Zhao, Changjing Zhou, Guodong Chen, Puyan Cao, Ruibing |
author_facet | Niu, Jichen Jiang, Ya Xu, Hao Zhao, Changjing Zhou, Guodong Chen, Puyan Cao, Ruibing |
author_sort | Niu, Jichen |
collection | PubMed |
description | Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, the leading cause of viral-induced encephalitis. Several host molecules have been identified as the JEV attachment factor; however, the molecules involved in JEV entry remain poorly understood. In the present study, we demonstrate that TIM-1 is important for efficient infection by JEV. Firstly, three TIM-1 variants (V1, V2, and V3) were cloned from A549 cells, and we revealed that only ectopically TIM-1 V2 expression in 293T cells significantly promotes JEV attachment, entry and infection. Point mutation of phosphatidylserine (Ptdser) binding pocket in the TIM-1 IgV domain dampened JEV entry, indicating that TIM-1-mediated JEV infection is Ptdser-dependent. Furthermore, we found the cytoplasmic domain of TIM-1 is also required for enhancing JEV entry. Additionally, knock down of TIM-1 expression in A549 cells impaired JEV entry and infection, but not attachment, suggesting that additional factors exist in A549 cells that allow the virus to bind. In conclusion, our findings demonstrate that TIM-1 promotes JEV infection as an entry cofactor, and the polymorphism of TIM-1 is associated with JEV susceptibility to host cells. |
format | Online Article Text |
id | pubmed-6265761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62657612018-12-07 TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection Niu, Jichen Jiang, Ya Xu, Hao Zhao, Changjing Zhou, Guodong Chen, Puyan Cao, Ruibing Viruses Article Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, the leading cause of viral-induced encephalitis. Several host molecules have been identified as the JEV attachment factor; however, the molecules involved in JEV entry remain poorly understood. In the present study, we demonstrate that TIM-1 is important for efficient infection by JEV. Firstly, three TIM-1 variants (V1, V2, and V3) were cloned from A549 cells, and we revealed that only ectopically TIM-1 V2 expression in 293T cells significantly promotes JEV attachment, entry and infection. Point mutation of phosphatidylserine (Ptdser) binding pocket in the TIM-1 IgV domain dampened JEV entry, indicating that TIM-1-mediated JEV infection is Ptdser-dependent. Furthermore, we found the cytoplasmic domain of TIM-1 is also required for enhancing JEV entry. Additionally, knock down of TIM-1 expression in A549 cells impaired JEV entry and infection, but not attachment, suggesting that additional factors exist in A549 cells that allow the virus to bind. In conclusion, our findings demonstrate that TIM-1 promotes JEV infection as an entry cofactor, and the polymorphism of TIM-1 is associated with JEV susceptibility to host cells. MDPI 2018-11-14 /pmc/articles/PMC6265761/ /pubmed/30441759 http://dx.doi.org/10.3390/v10110630 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Niu, Jichen Jiang, Ya Xu, Hao Zhao, Changjing Zhou, Guodong Chen, Puyan Cao, Ruibing TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection |
title | TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection |
title_full | TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection |
title_fullStr | TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection |
title_full_unstemmed | TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection |
title_short | TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection |
title_sort | tim-1 promotes japanese encephalitis virus entry and infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265761/ https://www.ncbi.nlm.nih.gov/pubmed/30441759 http://dx.doi.org/10.3390/v10110630 |
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