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Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-? and IFN inducer.

ABSTRACT: OBJECTIVES:Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking. METHODS:We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV. RESULTS:Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10?U/mL interferon-? (IFN?) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFN? and IFN inducer than SARS-CoV in Calu3. CONCLUSIONS:Despite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.

SUBMITTER: Shuai H

PROVIDER: S-EPMC7373021 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer.

Shuai Huiping H Chu Hin H Hou Yuxin Y Yang Dong D Wang Yixin Y Hu Bingjie B Huang Xiner X Zhang Xi X Chai Yue Y Cai Jian-Piao JP Chan Jasper Fuk-Woo JF Yuen Kwok-Yung KY

The Journal of infection 20200721 4

<h4>Objectives</h4>Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking.<h4>Methods</h4>We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Ca ...[more]

PMID: 32707230

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Project description:BackgroundThe SARS-CoV-2 infection has spread at an alarming rate with many places showing multiple peaks in incidence. Present study analyzes a total of 332 SARS-CoV-2 genome sequences from 114 asymptomatic and 218 deceased patients from twenty-one different countries to assess the mutation profile therein in order to establish the correlation between the clinical status and the observed mutations.MethodsThe mining of mutations was carried out using the GISAID CoVSurver (www.gisaid.org/epiflu-applications/covsurver-mutations-app) with the reference sequence 'hCoV-19/Wuhan/WIV04/2019' present in NCBI with Accession number NC-045512.2. The impact of the mutations on SARS-CoV-2 proteins mutation was predicted using PredictSNP1(loschmidt.chemi.muni.cz/predictsnp1) which is a meta-server integrating six predictor tools: SIFT, PhD-SNP, PolyPhen-1, PolyPhen-2, MAPP and SNAP. The iStable integrated server (predictor.nchu.edu.tw/iStable) was used to predict shifts in the protein stability due to mutations.ResultsA total of 372 variants were observed in the 332 SARS-CoV-2 sequences with several variants present in multiple patients accounting for a total of 1596 incidences. Asymptomatic and deceased specific mutants constituted 32% and 62% of the repertoire respectively indicating their partial exclusivity. However, the most prevalent mutations were those present in both. Though some parts of the genome are more variable than others but there was clear difference between incidence and prevalence. Non-structural protein 3 (NSP3) with 68 variants had a total of only 105 incidences whereas Spike protein had 346 incidences with just 66 variants. Amongst the Deleterious variants, NSP3 had the highest incidence of 25 followed by NSP2 (16), ORF3a (14) and N (14). Spike protein had just 7 Deleterious variants out of 66.ConclusionDeceased patients have more Deleterious than Neutral variants as compared to the asymptomatic ones. Further, it appears that the Deleterious variants which decrease protein stability are more significant in pathogenicity of SARS-CoV-2.

Dataset Information

Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-? and IFN inducer.

Publications

Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer.

Similar Datasets

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