Viruses (Aug 2022)

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

  • Rui Xiong,
  • Rui Fu,
  • Yong Wu,
  • Xi Wu,
  • Yuan Cao,
  • Zhe Qu,
  • Yanwei Yang,
  • Susu Liu,
  • Guitao Huo,
  • Sanlong Wang,
  • Weijin Huang,
  • Jianjun Lyu,
  • Xiang Zhu,
  • Chunnan Liang,
  • Yihong Peng,
  • Youchun Wang,
  • Changfa Fan

DOI
https://doi.org/10.3390/v14081740
Journal volume & issue
Vol. 14, no. 8
p. 1740

Abstract

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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.

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