Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection <i>In Vitro</i> , despite Eliciting a Prolonged Antiviral Response

生物 转录组 病毒学 病毒复制 免疫学 免疫系统 病毒 人口 病毒释放 干扰素 肿瘤坏死因子α 细胞 基因 基因表达 医学 遗传学 环境卫生
作者
Akshamal M. Gamage,Kai Tan,Wharton O. Y. Chan,Zhe Zhang Ryan Lew,Jing Liu,Chee Pin Tan,Deepa Rajagopalan,Quy Xiao Xuan Lin,Le Thanh Tan,Prasanna K. Venkatesh,Yew-Soon Ong,Mark Thong,Raymond T. P. Lin,Shyam Prabhakar,De Yun Wang,Lin-Fa Wang
出处
期刊:MBio [American Society for Microbiology]
卷期号:13 (1) 被引量:8
标识
DOI:10.1128/mbio.03436-21
摘要

The dynamics of SARS-CoV-2 infection in COVID-19 patients are highly variable, with a subset of patients demonstrating prolonged virus shedding, which poses a significant challenge for disease management and transmission control. In this study, the long-term dynamics of SARS-CoV-2 infection were investigated using a human well-differentiated nasal epithelial cell (NEC) model of infection. NECs were observed to release SARS-CoV-2 virus onto the apical surface for up to 28 days postinfection (dpi), further corroborated by viral antigen staining. Single-cell transcriptome sequencing (sc-seq) was utilized to explore the host response from infected NECs after short-term (3-dpi) and long-term (28-dpi) infection. We identified a unique population of cells harboring high viral loads present at both 3 and 28 dpi, characterized by expression of cell stress-related genes DDIT3 and ATF3 and enriched for genes involved in tumor necrosis factor alpha (TNF-α) signaling and apoptosis. Remarkably, this sc-seq analysis revealed an antiviral gene signature within all NEC cell types even at 28 dpi. We demonstrate increased replication of basal cells, absence of widespread cell death within the epithelial monolayer, and the ability of SARS-CoV-2 to replicate despite a continuous interferon response as factors likely contributing to SARS-CoV-2 persistence. This study provides a model system for development of therapeutics aimed at improving viral clearance in immunocompromised patients and implies a crucial role for immune cells in mediating viral clearance from infected epithelia. IMPORTANCE Increasing medical attention has been drawn to the persistence of symptoms (long-COVID syndrome) or live virus shedding from subsets of COVID-19 patients weeks to months after the initial onset of symptoms. In vitro approaches to model viral or symptom persistence are needed to fully dissect the complex and likely varied mechanisms underlying these clinical observations. We show that in vitro differentiated human NECs are persistently infected with SARS-CoV-2 for up to 28 dpi. This viral replication occurred despite the presence of an antiviral gene signature across all NEC cell types even at 28 dpi. This indicates that epithelial cell intrinsic antiviral responses are insufficient for the clearance of SARS-CoV-2, implying an essential role for tissue-resident and infiltrating immune cells for eventual viral clearance from infected airway tissue in COVID-19 patients.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
秋夜临完成签到,获得积分10
11秒前
菠萝蜜完成签到 ,获得积分10
12秒前
isedu完成签到,获得积分10
23秒前
啥时候能早睡完成签到 ,获得积分10
23秒前
Jonsnow完成签到 ,获得积分10
28秒前
wefor完成签到 ,获得积分10
38秒前
zyw完成签到 ,获得积分10
43秒前
传奇完成签到 ,获得积分10
46秒前
霸气白曼完成签到 ,获得积分10
49秒前
李彪完成签到 ,获得积分0
52秒前
jjy完成签到,获得积分10
53秒前
J陆lululu完成签到 ,获得积分10
1分钟前
jj824完成签到 ,获得积分10
1分钟前
Arthur完成签到,获得积分10
1分钟前
Wayne72完成签到,获得积分10
1分钟前
张占完成签到,获得积分10
1分钟前
1分钟前
nteicu发布了新的文献求助10
1分钟前
明朗完成签到 ,获得积分10
1分钟前
糊涂的乞完成签到 ,获得积分20
1分钟前
大水完成签到 ,获得积分10
1分钟前
zzr完成签到 ,获得积分10
1分钟前
TerryWei完成签到 ,获得积分10
1分钟前
苇一完成签到,获得积分10
1分钟前
loren313完成签到,获得积分10
2分钟前
Guo完成签到 ,获得积分10
2分钟前
俊逸灵松完成签到 ,获得积分10
2分钟前
坚强的缘分完成签到 ,获得积分10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
童童应助科研通管家采纳,获得10
2分钟前
勤奋凡之完成签到 ,获得积分10
2分钟前
波波完成签到 ,获得积分10
2分钟前
hongt05完成签到 ,获得积分10
2分钟前
又又完成签到,获得积分10
3分钟前
TORCH完成签到 ,获得积分10
3分钟前
想吃麻辣烫完成签到 ,获得积分10
3分钟前
SAINT完成签到 ,获得积分10
3分钟前
终究是残念完成签到,获得积分10
3分钟前
mj完成签到 ,获得积分10
3分钟前
鬼道众完成签到 ,获得积分10
3分钟前
高分求助中
Un calendrier babylonien des travaux, des signes et des mois: Séries iqqur îpuš 1036
Sustainable Land Management: Strategies to Cope with the Marginalisation of Agriculture 1000
Corrosion and Oxygen Control 600
Python Programming for Linguistics and Digital Humanities: Applications for Text-Focused Fields 500
Heterocyclic Stilbene and Bibenzyl Derivatives in Liverworts: Distribution, Structures, Total Synthesis and Biological Activity 500
重庆市新能源汽车产业大数据招商指南(两链两图两池两库两平台两清单两报告) 400
Division and square root. Digit-recurrence algorithms and implementations 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2546041
求助须知:如何正确求助?哪些是违规求助? 2175672
关于积分的说明 5600229
捐赠科研通 1896383
什么是DOI,文献DOI怎么找? 946268
版权声明 565379
科研通“疑难数据库(出版商)”最低求助积分说明 503557