Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus
Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2-/- mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 109.8 copies/g and 1c106 TCID50 in nasal cavity, as well as 1 × 108 copies/g and 1 × 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2-/- mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2-/- mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Viruses - 14(2022), 8 vom: 09. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiong, Rui [VerfasserIn] |
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| Links: |
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| Themen: |
CRISPR/Cas9 |
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| Anmerkungen: |
Date Completed 29.08.2022 Date Revised 02.09.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/v14081740 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345347560 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2-/- mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 109.8 copies/g and 1c106 TCID50 in nasal cavity, as well as 1 × 108 copies/g and 1 × 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2-/- mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2-/- mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a CRISPR/Cas9 | |
| 650 | 4 | |a Rag2−/− mice | |
| 650 | 4 | |a T and B cell deficiency | |
| 650 | 4 | |a host immune response | |
| 650 | 4 | |a human respiratory syncytial virus | |
| 700 | 1 | |a Fu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yanwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Susu |e verfasserin |4 aut | |
| 700 | 1 | |a Huo, Guitao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Sanlong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Weijin |e verfasserin |4 aut | |
| 700 | 1 | |a Lyu, Jianjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Chunnan |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Yihong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youchun |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Changfa |e verfasserin |4 aut | |
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