Mortimer B. Zuckerman Mind, and Brain and Behavior Institute, Columbia University, New York, NY 10027, USA.
Mortimer B. Zuckerman Mind, and Brain and Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Genetics and Development, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Cell. 2022 Mar 17;185(6):1052-1064.e12. doi: 10.1016/j.cell.2022.01.024. Epub 2022 Feb 2.
SARS-CoV-2 infects less than 1% of cells in the human body, yet it can cause severe damage in a variety of organs. Thus, deciphering the non-cell-autonomous effects of SARS-CoV-2 infection is imperative for understanding the cellular and molecular disruption it elicits. Neurological and cognitive defects are among the least understood symptoms of COVID-19 patients, with olfactory dysfunction being their most common sensory deficit. Here, we show that both in humans and hamsters, SARS-CoV-2 infection causes widespread downregulation of olfactory receptors (ORs) and of their signaling components. This non-cell-autonomous effect is preceded by a dramatic reorganization of the neuronal nuclear architecture, which results in dissipation of genomic compartments harboring OR genes. Our data provide a potential mechanism by which SARS-CoV-2 infection alters the cellular morphology and the transcriptome of cells it cannot infect, offering insight to its systemic effects in olfaction and beyond.
SARS-CoV-2 仅感染人体不到 1%的细胞，但它可导致多种器官严重损伤。因此，解析 SARS-CoV-2 感染的非细胞自主效应对理解其引发的细胞和分子紊乱至关重要。神经和认知缺陷是 COVID-19 患者中最不为人知的症状之一，嗅觉功能障碍是他们最常见的感觉缺失。在这里，我们发现，在人类和仓鼠中，SARS-CoV-2 感染都会导致嗅觉受体（OR）及其信号成分的广泛下调。这种非细胞自主效应之前是神经元核结构的剧烈重组，导致包含 OR 基因的基因组区室耗散。我们的数据提供了一种潜在的机制，通过该机制，SARS-CoV-2 感染改变了其无法感染的细胞的形态和转录组，为其在嗅觉及其他方面的全身效应提供了深入了解。
