Langsjoen Rose M, Zhou Yiyang, Holcomb Richard J, Routh Andrew L
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas.
Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas.
Am J Trop Med Hyg. 2021 Nov 29;106(1):99-104. doi: 10.4269/ajtmh.21-0719.
Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen in family Togaviridae, genus Alphavirus. Although CHIKV is well known for its ability to cause debilitating rheumatoid-like arthritis, it has been also been observed to cause cardiovascular symptoms such as arrhythmias. Here, using samples from a previous study, we sequenced RNA from serum, kidney, skeletal muscle, and cardiac muscle from CHIKV- and mock-infected IFN-αR-/- mice using two sequencing techniques to investigate heart-specific changes in virus mutational profiles and host gene expression. Mutation rates were similar across muscle tissues although heart tissue carried heart-specific CHIKV minority variants, one of which had a coding change in the nsP3 gene and another in the 3'UTR. Importantly, heart-specific transcriptional changes included differential expression of genes critical for ion transport and muscle contraction. These results demonstrate that CHIKV replicates in the hearts of immunodeficient mice and induce heart-specific mutations and host responses with implications for cardiac pathologies.
基孔肯雅病毒(CHIKV)是披膜病毒科甲病毒属中一种由蚊子传播的病原体。尽管CHIKV以其引发使人衰弱的类风湿样关节炎的能力而闻名,但也有人观察到它会导致心律失常等心血管症状。在此,我们使用之前一项研究中的样本,通过两种测序技术对CHIKV感染组和模拟感染组的IFN-αR-/-小鼠的血清、肾脏、骨骼肌和心肌中的RNA进行测序,以研究病毒突变谱和宿主基因表达的心脏特异性变化。尽管心脏组织携带心脏特异性的CHIKV少数变异体,其中一个在nsP3基因中有编码变化,另一个在3'UTR中,但肌肉组织中的突变率相似。重要的是,心脏特异性转录变化包括对离子转运和肌肉收缩至关重要的基因的差异表达。这些结果表明,CHIKV在免疫缺陷小鼠的心脏中复制,并诱导心脏特异性突变和宿主反应,这对心脏病理学具有重要意义。