SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model.
SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model.
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DOI：
10.1126/scisignal.ade4984
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发表时间：
2023-05-09
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
尽管SARS-CoV-2感染主要局限于呼吸道，但它与感觉异常有关，这种异常表现在急性和慢性两种表型上。为了深入了解这些感觉异常的分子基础，我们使用金黄地鼠模型来表征和比较感染SARS-CoV-2和甲型流感病毒(IAV)对感觉神经系统的影响。在病毒鼻腔感染的前24小时内，我们在颈、胸脊髓和背根节(DRGs)中检测到SARS-CoV-2转录本，但没有感染性物质。感染SARS-CoV-2的仓鼠表现出机械过敏，与感染IAV的仓鼠相比，这种过敏较温和，但持续时间较长。对感染后1-4天的胸腔DRG的RNA测序分析表明，在感染SARS-CoV-2的动物中，主要是神经元信号的扰动，而在IAV感染的动物中，I型干扰素信号是相反的。感染31天后，SARS-CoV-2感染动物的胸椎DRG中出现了一个神经病理性转录组，这与SARS-CoV-2特异性的机械超敏反应相吻合。这些数据揭示了疼痛管理的潜在靶点，包括RNA结合蛋白ILF3，它在小鼠疼痛模型中得到了验证。这项工作阐明了SARS-CoV-2引发的DRG中的转录信号，可能是短期和长期感觉异常的基础。
Although largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and chronic phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster model to characterize and compare the effects of infection with SARS-CoV-2 and Influenza A virus (IAV) on the sensory nervous system. We detected SARS-CoV-2 transcripts but no infectious material in the cervical and thoracic spinal cord and dorsal root ganglia (DRGs) within the first 24 hours of intranasal virus infection. SARS-CoV-2–infected hamsters exhibited mechanical hypersensitivity that was milder but prolonged compared to that observed in IAV-infected hamsters. RNA sequencing analysis of thoracic DRGs 1 to 4 days after infection suggested perturbations in predominantly neuronal signaling in SARS-CoV-2–infected animals as opposed to type I interferon signaling in IAV-infected animals. Later, 31 days after infection, a neuropathic transcriptome emerged in thoracic DRGs from SARS-CoV-2–infected animals, which coincided with SARS-CoV-2–specific mechanical hypersensitivity. These data revealed potential targets for pain management, including the RNA-binding protein ILF3, which was validated in murine pain models. This work elucidates transcriptomic signatures in the DRGs triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities.
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影响因子：
17.1
作者：
Frere, Justin J.;Serafini, Randal A.;Pryce, Kerri D.;Zazhytska, Marianna;Oishi, Kohei;Golynker, Ilona;Panis, Maryline;Zimering, Jeffrey;Horiuchi, Shu;Hoagland, Daisy A.;Moller, Rasmus;Ruiz, Anne;Kodra, Albana;Overdevest, Jonathan B.;Canoll, Peter D.;Borczuk, Alain C.;Chandar, Vasuretha;Bram, Yaron;Schwartz, Robert;Lomvardas, Stavros;Zachariou, Venetia;Tenoever, Benjamin R.
通讯作者：
Tenoever, Benjamin R.
影响因子：
3.7
作者：
Elliott R;Li F;Dragomir I;Chua MM;Gregory BD;Weiss SR
通讯作者：
Weiss SR
影响因子：
8.3
作者：
Escalard, Simon;Chalumeau, Vanessa;Piotin, Michel
通讯作者：
Piotin, Michel
影响因子：
7.4
作者：
通讯作者：
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影响因子：
7.4
作者：
Fernandez-de-las-Penas, Cesar;De-la-Llave-Rincon, Ana, I;Arendt-Nielsen, Lars
通讯作者：
Arendt-Nielsen, Lars