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
Affiliations
Rui Xiong
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Rui Fu
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Yong Wu
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Xi Wu
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Yuan Cao
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Zhe Qu
National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China
Yanwei Yang
National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China
Susu Liu
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Guitao Huo
National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China
Sanlong Wang
National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China
Weijin Huang
Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Jianjun Lyu
Department of Pathology, InnoStar Bio-Tech Nantong Co., Ltd., Nantong 226133, China
Xiang Zhu
Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Chunnan Liang
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Yihong Peng
Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Youchun Wang
Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
Changfa Fan
National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China
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.
