IL2rg-/- rats support prolonged infection of human RSV
10.3969/j.issn.1005-4847.2024.01.003
- VernacularTitle:IL2rg-/-大鼠支持人RSV在体内的长期感染
- Author:
Rui XIONG
1
,
2
;
Yong WU
;
Yanwei YANG
;
Zhe QU
;
Susu LIU
;
Yuya WANG
;
Liying MA
;
Rui FU
;
Yihong PENG
;
Chunnan LIANG
;
Changfa FAN
Author Information
1. 中国食品药品检定研究院实验动物资源研究所(国家啮齿类实验动物资源库),北京 102629
2. 北京大学医学部基础医学院病原生物学系,北京 100083
- Keywords:
IL2rg-/-rat;
TALEN technology;
NK cell defects;
human respiratory syncytial virus;
infection animal model
- From:
Acta Laboratorium Animalis Scientia Sinica
2024;32(1):17-24
- CountryChina
- Language:Chinese
-
Abstract:
Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0~35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.