Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus

被引：7

作者：

Xiong, Rui ^{[1
,2
,3
]}

Fu, Rui ^{[1
]}

Wu, Yong ^{[1
]}

Wu, Xi ^{[1
]}

Cao, Yuan ^{[1
]}

Qu, Zhe ^{[4
]}

Yang, Yanwei ^{[4
]}

Liu, Susu ^{[1
]}

Huo, Guitao ^{[4
]}

Wang, Sanlong ^{[4
]}

Huang, Weijin ^{[5
]}

Lyu, Jianjun ^{[6
]}

Zhu, Xiang ^{[2
,3
]}

Liang, Chunnan ^{[1
]}

Peng, Yihong ^{[2
,3
]}

Wang, Youchun ^{[5
]}

Fan, Changfa ^{[1
]}

机构：

[1] Natl Inst Food & Drug Control, Inst Lab Anim Resources, Natl Rodent Lab Anim Resources Ctr, Beijing 102629, Peoples R China

[2] Peking Univ, Sch Basic Med Sci, Dept Microbiol, Hlth Sci Ctr, Beijing 100083, Peoples R China

[3] Peking Univ, Sch Basic Med Sci, Ctr Infect Dis, Hlth Sci Ctr, Beijing 100083, Peoples R China

[4] Natl Inst Food & Drug Control, Natl Ctr Safety Evaluat Drugs, Inst Food & Drug Safety Evaluat, Beijing 100176, Peoples R China

[5] Natl Inst Food & Drug Control, Div HIV AIDS & Sexually Transmitted Virus Vaccine, Inst Biol Prod Control, Beijing 102629, Peoples R China

[6] InnoStar Bio Tech Nantong Co Ltd, Dept Pathol, Nantong 226133, Peoples R China

来源：

VIRUSES-BASEL | 2022年 / 14卷 / 08期

基金：

国家重点研发计划;

关键词：

human respiratory syncytial virus; Rag2(- -) mice; CRISPR; Cas9; T and B cell deficiency; host immune response; VIRAL REPLICATION; EXPRESSION; INFANTS; DISEASE; DAMAGE; INTERLEUKIN-1; STIMULATION; FIBROBLASTS; CHIMPANZEES; CYTOKINES;

D O I：

10.3390/v14081740

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 x 10(9.8) copies/g and 1c10(6) TCID50 in nasal cavity, as well as 1 x 10(8) copies/g and 1 x 10(5) 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.

引用

页数：13

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