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T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) is the causative agent of a potentially fatal neurological infection affecting humans. The host factors required for viral entry have yet to be described. Here, we found that T-cell immunoglobulin and mucin domain 1 (TIM-1) acted as the cellular entry factor for...

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Autores principales: Zhang, Xiaowei, Liang, Cuiqin, Wang, Hanzhong, Guo, Zhengyuan, Rong, Heng, Pan, Jingdi, Li, Wei, Pei, Rongjuan, Chen, Xinwen, Zhang, Zhiping, Zhang, Xian-En, Cui, Zongqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787471/
https://www.ncbi.nlm.nih.gov/pubmed/35073759
http://dx.doi.org/10.1128/mbio.02860-21
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author Zhang, Xiaowei
Liang, Cuiqin
Wang, Hanzhong
Guo, Zhengyuan
Rong, Heng
Pan, Jingdi
Li, Wei
Pei, Rongjuan
Chen, Xinwen
Zhang, Zhiping
Zhang, Xian-En
Cui, Zongqiang
author_facet Zhang, Xiaowei
Liang, Cuiqin
Wang, Hanzhong
Guo, Zhengyuan
Rong, Heng
Pan, Jingdi
Li, Wei
Pei, Rongjuan
Chen, Xinwen
Zhang, Zhiping
Zhang, Xian-En
Cui, Zongqiang
author_sort Zhang, Xiaowei
collection PubMed
description Tick-borne encephalitis virus (TBEV) is the causative agent of a potentially fatal neurological infection affecting humans. The host factors required for viral entry have yet to be described. Here, we found that T-cell immunoglobulin and mucin domain 1 (TIM-1) acted as the cellular entry factor for TBEV. Using a virus overlay protein binding assay, TIM-1 was identified as a virion-interacting protein. Cells that were relatively resistant to TBEV infection became highly susceptible to infection when TIM-1 was ectopically expressed. TIM-1 knockout and viral RNA bypass assays showed that TIM-1 functioned in the entry phase of TBEV infection. TIM-1 mediated TBEV uptake and was cointernalized with virus particles into the cell. Antibodies for TIM-1, soluble TIM-1, or TIM-1 knockdown significantly inhibited TBEV infection in permissive cells. Furthermore, in TIM-1 knockout mice, TIM-1 deficiency markedly lowered viral burden and reduced mortality and morbidity, highlighting the functional relevance of TIM-1 in vivo. With TIM-1, we have identified a key host factor for TBEV entry and a potential target for antiviral intervention.
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spelling pubmed-87874712022-02-07 T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus Zhang, Xiaowei Liang, Cuiqin Wang, Hanzhong Guo, Zhengyuan Rong, Heng Pan, Jingdi Li, Wei Pei, Rongjuan Chen, Xinwen Zhang, Zhiping Zhang, Xian-En Cui, Zongqiang mBio Research Article Tick-borne encephalitis virus (TBEV) is the causative agent of a potentially fatal neurological infection affecting humans. The host factors required for viral entry have yet to be described. Here, we found that T-cell immunoglobulin and mucin domain 1 (TIM-1) acted as the cellular entry factor for TBEV. Using a virus overlay protein binding assay, TIM-1 was identified as a virion-interacting protein. Cells that were relatively resistant to TBEV infection became highly susceptible to infection when TIM-1 was ectopically expressed. TIM-1 knockout and viral RNA bypass assays showed that TIM-1 functioned in the entry phase of TBEV infection. TIM-1 mediated TBEV uptake and was cointernalized with virus particles into the cell. Antibodies for TIM-1, soluble TIM-1, or TIM-1 knockdown significantly inhibited TBEV infection in permissive cells. Furthermore, in TIM-1 knockout mice, TIM-1 deficiency markedly lowered viral burden and reduced mortality and morbidity, highlighting the functional relevance of TIM-1 in vivo. With TIM-1, we have identified a key host factor for TBEV entry and a potential target for antiviral intervention. American Society for Microbiology 2022-01-25 /pmc/articles/PMC8787471/ /pubmed/35073759 http://dx.doi.org/10.1128/mbio.02860-21 Text en Copyright © 2022 Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Zhang, Xiaowei
Liang, Cuiqin
Wang, Hanzhong
Guo, Zhengyuan
Rong, Heng
Pan, Jingdi
Li, Wei
Pei, Rongjuan
Chen, Xinwen
Zhang, Zhiping
Zhang, Xian-En
Cui, Zongqiang
T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus
title T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus
title_full T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus
title_fullStr T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus
title_full_unstemmed T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus
title_short T-Cell Immunoglobulin and Mucin Domain 1 (TIM-1) Is a Functional Entry Factor for Tick-Borne Encephalitis Virus
title_sort t-cell immunoglobulin and mucin domain 1 (tim-1) is a functional entry factor for tick-borne encephalitis virus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787471/
https://www.ncbi.nlm.nih.gov/pubmed/35073759
http://dx.doi.org/10.1128/mbio.02860-21
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