1. m 6 A Reader YTHDC1 Impairs Respiratory Syncytial Virus Infection by Downregulating Membrane CX3CR1 Expression.
- Author
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Picavet LW, van Vroonhoven ECN, Scholman RC, Smits YTH, Banerjee R, Besteman SB, Viveen MC, van der Vlist MM, Tanenbaum ME, Lebbink RJ, Vastert SJ, and van Loosdregt J
- Subjects
- Humans, A549 Cells, Adenosine analogs & derivatives, Adenosine metabolism, Cell Line, Epithelial Cells virology, Epithelial Cells metabolism, Host-Pathogen Interactions, Methylation, Nerve Tissue Proteins, Respiratory Syncytial Virus, Human physiology, RNA, Viral genetics, RNA, Viral metabolism, Virus Internalization, Virus Replication, CX3C Chemokine Receptor 1 metabolism, CX3C Chemokine Receptor 1 genetics, Down-Regulation, Respiratory Syncytial Virus Infections virology, Respiratory Syncytial Virus Infections metabolism, RNA Splicing Factors metabolism, RNA Splicing Factors genetics
- Abstract
Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, N6-methyladenosine (m
6 A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m6 A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m6 A is also involved in viral entry and whether m6 A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m6 A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m6 A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.- Published
- 2024
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