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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.
These authors contributed equally to this work.
Financial support: This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award NRSA (TL1) Training Core (TL1TR001440) from the National Center for Advancing Translational Sciences, National Institutes of Health. R. M. L. was additionally supported by the Jeanne B. Kempner postdoctoral fellowship through the University of Texas Medical Branch, Galveston. Funding for sequencing was provided by start-up funds from the University of Texas Medical Branch.
Authors’ addresses: Rose M. Langsjoen, Yiyang Zhou, and Richard J. Holcomb, University of Texas Medical Branch, Galveston, TX, E-mails: firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org. Andrew L. Routh, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, TX, and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, E-mail: email@example.com.