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

Author:

Xiong RuiORCID,Fu Rui,Wu Yong,Wu Xi,Cao Yuan,Qu Zhe,Yang Yanwei,Liu Susu,Huo Guitao,Wang Sanlong,Huang WeijinORCID,Lyu Jianjun,Zhu Xiang,Liang ChunnanORCID,Peng YihongORCID,Wang YouchunORCID,Fan Changfa

Abstract

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.

Funder

the National Key R&D Program of China

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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