The Identification of Rhinovirus C Susceptible Inbred Mice
Refereed conference paper presented and published in conference proceedings



摘要RATIONALE Human rhinovirus (RV) infection is the leading respiratory virus causing respiratory tract infections and it precedes a higher prevalence in children with asthmaexacerbations than those with controlled asthma. RV-C attracts our research attention, as it has an extended niche in causing bronchiolitis, pneumonia and shared the responsibilitywith RV-A in their association with wheezing illness and asthma exacerbation. Because of the unavailability of the infectious RV-C stock, there is never an attempt to develop small-animal models for RV-C. This hinders the investigations of RV-C pathogenesis and the development of RV-C therapeutics. By transfecting the RV-C15 reverse transcribed plasmidinto a mouse lung epithelial cells (LA-4), replication of RV-C was observed indicating that the cellular machinery could support the replication of RV-C in murine airway respiratorycells. With this clue, we attempted to identify a RV-C susceptible in vivo mouse model. METHODS Nine different inbred strains of a discrete set of inbred strains that captures anespecially broad genetic diversity (A/J, Balb/c, CAST/Ei, C57BL/6, NOD/ShiLt, NZO/HiLt, PWK/Ph, WSB/Ei, and 129S1/SvIm) were selected for this project. Fifteen mice at 6-to-8weeks old of each strain were infected with 50ul of genetically engineered eGFP-RV-C15 by intratracheal inoculation. A MEM inoculated group was as control in Balb/c strain. TheRV-C15 infection in the mouse lung was evaluated by the detection of viral gene copy number in the lung homogenate at 0, 24, 72 hours post-infection (hpi). The absolute viral genecopy number was extrapolated from a serial dilution of a standard plasmid with known copy number and normalized with the copy number of the housekeeping gene (beta-actin).Individual point on the figures represent one mouse at that time point and each mouse just contributed one data point as they were sacrificed for lung harvesting. RESULTSWSB/EiJ had an increasing trend of viral gene copy number from inoculation to 24 hpi while PWK strains had an increasing trend of viral load from 24-to-72 hpi (3 out of 5) (Fig A,susceptible). CAST and NOD/ShiLTJ gave a steady viral copy number across all time points (Fig B, subtle-infection). While the viral load in the lung homogenates of the mousestrains grouped as non-susceptible, namely A/J, Balb/c, C57BL/6, NZO/HiLt, and 129S1/SvIm, dropped directly to the undetectable level at 24 hpi (Fig C, unsusceptible).CONCLUSION WSB/EiJ and PWK strains could be served as a RV-C susceptible in vivo model for the RV-C pathogenesis study.
著者W. Chan, I. Martin, K. Tao, T. Li, J. Tsun, W. Yu, G. Wong, J. P. Mizgerd
會議名稱International Conference of the American-Thoracic-Society (ATS2019)

上次更新時間 2021-19-09 於 00:46