PDF(Pubmed)
Abstract：
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
摘要：
严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的病毒载量和病毒脱落的持续时间是2019年冠状病毒病传播的重要决定因素。在这项研究中,我们通过时间组织学和转录分析检查了病毒剂量对K18-hACE2转基因小鼠肺和脾的影响。大约,SARS-CoV-2的1×105个斑块形成单位（PFU）从接种后2天（dpi）开始在肺部引起强烈的宿主反应，直到小鼠死亡才恢复。而对病毒的反应在5天很明显，在1×102PFU下以14dpi恢复到基础状态。Further,流式细胞术显示，1×102PFU病毒感染的肺部CD8+T细胞数量从2dpi开始持续增加，但在1×105PFU病毒感染的肺部没有。在脾脏中，从2dpi开始对病毒的反应突出，在1×105PFU时，B细胞数量显着减少；然而，1×102PFU的病毒从2dpi诱导了非常弱的反应，并恢复了10dpi。尽管防御反应恢复正常，老鼠幸存下来，肺组织学显示纤维化的证据，提示SARS-CoV-2感染的后遗症。我们的发现表明，对SARS-CoV-2剂量的反应，肺和脾脏中免疫反应的特异性效应子增加或减少。这项研究表明，局部和全身免疫效应物对病毒感染的反应随病毒剂量而变化。这会加剧感染的严重程度或加速其消除。
