Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity.
Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity.
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DOI：
10.1016/j.immuni.2021.01.017
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发表时间：
2021-03-09
期刊：
影响因子：
32.4
通讯作者：
tenOever BR
中科院分区：
文献类型：
--
作者：
Hoagland DA;Møller R;Uhl SA;Oishi K;Frere J;Golynker I;Horiuchi S;Panis M;Blanco-Melo D;Sachs D;Arkun K;Lim JK;tenOever BR
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的出现和传播已导致全球严重发病率、死亡率和社会混乱。更好地了解病毒与宿主的相互作用可能会增强对限制这种感染的治疗见解。本研究通过组织学分析和转录谱分析研究了仓鼠对SARS-CoV-2的全身反应动力学。感染导致上呼吸道和下呼吸道持续高水平的病毒，并在其他远端组织中散发。一项纵向队列研究揭示了一波炎症，包括I型干扰素（IFN-I）反应，这在所有组织中都很明显，无论病毒是否存在，但不足以预防疾病进展。通过鼻内给药重组IFN-I增强抗病毒反应，减少病毒疾病，防止传播，并降低体内炎症。本研究定义了宿主对SARS-CoV-2感染的全身反应，并支持使用鼻内IFN-I作为早期治疗的有效手段。宿主对SARS-CoV-2的反应会导致严重的炎症。为了理解这种生物学，Hoagland等人利用受感染的仓鼠纵向地阐明了跨组织的转录足迹，显示了急性复制位点以外的炎症反应。局部给药IFN-I可减少病毒载量并改善免疫浸润。
The emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant global morbidity, mortality, and societal disruption. A better understanding of virus-host interactions may potentiate therapeutic insights toward limiting this infection. Here we investigated the dynamics of the systemic response to SARS-CoV-2 in hamsters by histological analysis and transcriptional profiling. Infection resulted in consistently high levels of virus in the upper and lower respiratory tracts and sporadic occurrence in other distal tissues. A longitudinal cohort revealed a wave of inflammation, including a type I interferon (IFN-I) response, that was evident in all tissues regardless of viral presence but was insufficient to prevent disease progression. Bolstering the antiviral response with intranasal administration of recombinant IFN-I reduced viral disease, prevented transmission, and lowered inflammation in vivo. This study defines the systemic host response to SARS-CoV-2 infection and supports use of intranasal IFN-I as an effective means of early treatment. The host response to SARS-CoV-2 results in significant inflammation. To understand this biology, Hoagland et al. utilize infected hamsters to elucidate transcriptional footprints across tissues longitudinally, showing an inflammatory response beyond the site of acute replication. Local administration of IFN-I reduces virus load and improves immune infiltrate.
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DOI：
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期刊：
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影响因子：
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作者：
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