OrganoVIR Labs, Emma Children's Hospital, Department of Pediatric Infectious Diseases, Amsterdam UMC, Academic Medical Center, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Reproduction and Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC, Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Nat Commun. 2024 Mar 21;15(1):2532. doi: 10.1038/s41467-024-46634-9.
Picornaviruses are a leading cause of central nervous system (CNS) infections. While genotypes such as parechovirus A3 (PeV-A3) and echovirus 11 (E11) can elicit severe neurological disease, the highly prevalent PeV-A1 is not associated with CNS disease. Here, we expand our current understanding of these differences in PeV-A CNS disease using human brain organoids and clinical isolates of the two PeV-A genotypes. Our data indicate that PeV-A1 and A3 specific differences in neurological disease are not due to infectivity of CNS cells as both viruses productively infect brain organoids with a similar cell tropism. Proteomic analysis shows that PeV-A infection significantly alters the host cell metabolism. The inflammatory response following PeV-A3 (and E11 infection) is significantly more potent than that upon PeV-A1 infection. Collectively, our findings align with clinical observations and suggest a role for neuroinflammation, rather than viral replication, in PeV-A3 (and E11) infection.
小核糖核酸病毒是中枢神经系统（CNS）感染的主要原因。虽然诸如肠道病毒 A3（PeV-A3）和柯萨奇病毒 11（E11）等基因型可引起严重的神经疾病，但高度流行的 PeV-A1 与 CNS 疾病无关。在这里，我们使用人脑类器官和两种 PeV-A 基因型的临床分离株，扩展了我们对这些 PeV-A CNS 疾病差异的现有认识。我们的数据表明，PeV-A1 和 A3 在神经疾病方面的特异性差异不是由于 CNS 细胞的感染性引起的，因为两种病毒都以相似的细胞嗜性在脑类器官中进行有效感染。蛋白质组学分析表明，PeV-A 感染会显著改变宿主细胞的代谢。PeV-A3（和 E11 感染）引起的炎症反应明显比 PeV-A1 感染更为强烈。总的来说，我们的发现与临床观察结果一致，并表明神经炎症而不是病毒复制在 PeV-A3（和 E11）感染中起作用。
