Dynamic Host Immune and Transcriptomic Responses to Respiratory Syncytial Virus Infection in a Vaccination-Challenge Mouse Model  

作　　者：Yu Zhao Chen Ma Jie Yang Xiufen Zou Zishu Pan 

机构地区：[1]State Key Laboratory of Virology,College of Life Sciences,Wuhan University,Wuhan,430072,China [2]School of Mathematics and Statistics,Wuhan University,Wuhan,430072,China

出　　处：《Virologica Sinica》2021年第6期1327-1340,共14页中国病毒学（英文版）

基　　金：This work was supported by the National key R&D program of China(2017YFA0505801);the National Natural Science Foundation of China(11831015)。

摘　　要：Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vaccinated infants upon subsequent natural RSV infection. The excessive inflammatory immunopathology in the lungs might be involved in the VED, but the underlying mechanisms remain not fully understood. In this study, we utilized UV-inactivated RSV in the prime/boost approach followed by RSV challenge in BALB/c mice to mimic RSV VED. The dynamic virus load,cytokines, histology and transcriptome profiles in lung tissues of mice were investigated from day 1 to day 6 post-infection.Compared to PBS-treated mice, UV-RSV vaccination leads to a Th2 type inflammatory response characterized by enhanced histopathology, reduced Treg cells and increased IL4^(+)CD4 T cells in the lung. Enhanced production of several Th2 type cytokines(IL-4, IL-5, IL-10) and TGF-b, reduction of IL-6 and IL-17 were observed in UV-RSV vaccinated mice. A total of 5582 differentially expressed(DE) genes between PBS-treated or vaccinated mice and na?ve mice were identified by RNA-Seq. Eleven conserved high-influential modules(HMs) were recognized, majorly grouped into regulatory networks related to cell cycle and cell metabolism, signal transduction, immune and inflammatory responses. At an early time post-infection, the vaccinated mice showed obvious decreased expression patterns of DE genes in 11 HMs compared to PBS-treated mice. The extracellular matrix(HM5) and immune responses(HM8) revealed tremendous differences in expression and regulation characteristics of transcripts between PBS-treated and vaccinated mice at both early and late time points. The highly connected genes in HM5 and HM8 networks were further validated by RT-qPCR.These findings reveal the relationship between RSV VED and immune responses, which could benefit the development of novel RSV vaccines.

关 键 词：Respiratory syncytial virus(RSV) Vaccine enhanced disease(VED) Transcriptome analysis Regulatory networks 

分 类 号：R392[医药卫生—免疫学]