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Schulz, Annika Lea

University of British Columbia

Despite the discovery of the ability of coronaviruses to infect neural cells over 25 years ago, the underlying molecular processes and the impact of coronavirus infection on these cells remain poorly characterized. The emergence of SARS-CoV-2 has brought renewed attention to the importance of understanding coronavirus neurotropism. In this study, we aimed to investigate the infectability of primary human astrocytes with both SARS-CoV-2 variants and the common cold coronavirus HCoV-229E. Given the robust infection that HCoV-229E established in astrocytes at 33°C, we hypothesized that this coronavirus elicits dynamic temporal dysregulation of both miRNA and mRNA expression in astrocytes. To test this hypothesis, we performed the first comprehensive transcriptomic analysis to profile the temporal changes in miRNA and mRNA expression patterns in response to HCoV-229E infection in astrocytes. The primary objective of this study was to identify key molecular pathways that undergo dysregulation over time in coronavirus-infected astrocytes. Specifically, we aimed to compare the miRNAs that are commonly dysregulated by SARS-CoV-2 infection in bronchial epithelial cells with those observed in HCoV-229E-infected astrocytes. By doing so, we sought to determine whether the regulatory response to coronavirus infection in astrocytes shares similarities with that of bronchial epithelial cells. Understanding these shared regulatory mechanisms could shed light on the broader implications of coronavirus infections in different cell types. Remarkably, both models exhibited limited miRNA dysregulation despite robust levels of viral propagation. Significantly, miR-4443 and miR-1246 exhibited notable upregulation during the late stages of infection in both models of coronavirus infection. In-depth analysis of miRNA-mRNA interactions in these distinct models revealed multiple distinctive interactions, underscoring the context-dependent regulatory function of miRNAs within the infected cells. This study reveals novel miRNA and mRNA targets involved in coronavirus-host interactions within astrocytes, potentially providing new therapeutic targets for combating coronavirus infections. Additionally, the identified molecular alterations induced by HCoV-229E in astrocytes could also have broader implications for our understanding of the neuropathology and potential long-term consequences of coronavirus infections. Overall, this study represents a significant step towards unravelling the complex interplay between coronaviruses and the human CNS, with potential implications for both viral pathogenesis and therapeutic strategies.

Text

2023-08-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/85597

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/