Innate immune responses triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play pivotal roles in the pathogenesis of COVID-19, while host factors including proinflammatory cytokines are critical for viral containment. By utilizing quantitative and qualitative models, we discovered that soluble factors secreted by human monocytes potently inhibit SARS-CoV-2-induced cell-cell fusion in viral-infected cells. Through cytokine screening, we identified that interleukin-1β (IL-1β), a key mediator of inflammation, inhibits syncytia formation mediated by various SARS-CoV-2 strains. Mechanistically, IL-1β activates RhoA/ROCK signaling through a non-canonical IL-1 receptor-dependent pathway, which drives the enrichment of actin bundles at the cell-cell junctions, thus prevents syncytia formation. Notably, in vivo infection experiments in mice confirmed that IL-1β significantly restricted SARS-CoV-2 spread in the lung epithelium. Together, by revealing the function and underlying mechanism of IL-1β on SARS-CoV-2-induced cell-cell fusion, our study highlights an unprecedented antiviral function for cytokines during viral infection.

The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is strongly resistant to extracellular therapeutic and convalescent antibodies via an unknown mechanism. Here, we describe the antibody-mediated spike activation and syncytia formation on cells displaying the viral spike. We found that soluble antibodies against receptor binding motif (RBM) are capable of inducing the proteolytic processing of spike at both the S1/S2 and S2' cleavage sites, hence triggering ACE2-independent cell-cell fusion. Mechanistically, antibody-induced cell-cell fusion requires the shedding of S1 and exposure of the fusion peptide at the cell surface. By inhibiting S1/S2 proteolysis, we demonstrated that cell-cell fusion mediated by spike can be re-sensitized towards antibody neutralization in vitro. Lastly, we showed that cytopathic effect mediated by authentic SARS-CoV-2 infection remain unaffected by the addition of extracellular neutralization antibodies. Hence, these results unveil a novel mode of antibody evasion and provide insights for antibody selection and drug design strategies targeting the SARS-CoV-2 infected cells.

ObjectiveTo isolate and study the biological characteristics of severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） from feces of coronavirus disease 2019 （COVID-19） patients.MethodsVero E6 cells were used for virus isolation and the isolated strains were tested by nucleic acid test， immunofluorescence test， virulence test and whole genome sequencing. 50% tissue culture infective dose （TCID50） was calculated after the cell cultures of each generation were collectedResultsEight fecal specimens were inoculated with Vero E6 cells after treatment and cultured for 48 h. One specimen showed obvious cytopathic effect on Vero E6 cells. One SARS-CoV-2 out of 8 fecal samples from COVID-19 patients were isolated， and separation rate was 12.5%. The TCID50 of P1， P2 and P3 were 104.0/0.2 mL， 104.5/0.2 mL and 104.75/0.2 mL， respectively. Only one of the 8 stool samples had SARS-CoV-2 virus replication and amplification， and the Ct value of the nucleic acid detection was about 10. The sequence of the isolation was more than 99.99% homologous with that of Wuhan-Hu-1（GenBank MN908947）.ConclusionThe SARS-CoV-2 strain is isolated from the fecal samples of COVID-19 cases and is confirmed by genomic sequencing and immunofluorescence test， which indicates the presence of live virus in feces of COVID-19 cases.

目的 研究2018-2020年上海市本地感染及输入性来源登革1型病毒(Dengue Serotype 1 virus,DENV-1)分离株全基因组序列特征.方法 收集登革热疑似病例血清样本,对DENV-1阳性样本进行病毒分离、全基因组扩增与测序,进一步通过构建进化树对全基因组序列进行同源性分析、核苷酸序列及氨基酸序列相似性分析、编码蛋白氨基酸位点差异分析.结果 从88份DENV-1阳性样本中获得31株分离株的全基因组核苷酸序列,其中3株为本地感染病例来源,28株为输入病例来源.进化分析显示,28株分离株的基因型为G-Ⅰ型,与G-Ⅰ型参考序列的核苷酸(氨基酸)相似性均值为96.47％～97.37％(98.78％～99.16％);3株分离株的基因型为G-Ⅳ型,与G-Ⅳ型参考序列的核苷酸(氨基酸)相似性均值为96.66％～96.86％(99.01％～99.26％);3株本地感染病例来源分离株均为G-Ⅰ型,根据同源性分析,存在输入性病例引起本地感染可能.分离株与对照株比较各结构蛋白与非结构蛋白氨基酸位点均存在差异,其中E蛋白的495个氨基酸位点中,有31个位点存在差异.结论 2018-2020年上海市DENV-1包含G-Ⅰ与G-Ⅳ两种基因型,以G-Ⅰ型为主;首次分离得到3株上海市本地感染病例来源DENV-1,为G-Ⅰ型,存在输入性病例引起本地感染可能.

The global spread of SARS-CoV-2 is currently continuing, and the World Health Organization has announced the risk assessment of the viruses as high. In this study, we analyzed virology features of SARS-CoV-2 causing a family cluster outbreak. Among the six family members, five have been laboratory-confirmed infection of SARS-CoV-2 viruses. A total of five SARS-CoV-2 viruses have been isolated from the nasopharyngeal swabs. The complete genome of the viruses exhibited 100% nucleotide identity with each other. Only two nucleotide differences have been observed between genomes of the isolated viruses and the HCoV/Wuhan/ IVDC-HB-01/2019 strain. Therefore, SARS-CoV-2 has been confirmed as the causation of the family cluster infections.

[目的]观察不同温度保存条件下细胞培养物中新型冠状病毒(简称"新冠病毒")存活情况,判断温度对病毒稳定性的影响,为新冠病毒肺炎疫情趋势研判及防控提供基础数据.[方法]将病毒接种于Vero E6细胞适应培养后,收获病毒液,根据所测得病毒半数组织培养感染剂量(TCID50)将不同稀释度(10-1、10-3、10-5、10-6)的病毒在不同温度下(4℃、22.5℃、37℃)保存1～7 d,并分别感染细胞,通过观察细胞病变效应(CPE)、实时荧光定量检测病毒核酸确定病毒感染性,以评价病毒在不同温度条件下的稳定性.[结果]不同浓度的新冠病毒在4℃条件下保存较为稳定,均具有感染性;22.5℃条件下,高浓度(10-1稀释度)病毒放置7d感染性逐渐下降,其他较低浓度病毒放置1d则完全失去感染性;37℃保存超过1d病毒即失去感染性.[结论]在细胞培养环境中,新冠病毒在4℃条件下高度稳定,对热敏感,且与病毒浓度相关,高浓度病毒室温22.5℃条件下仍可存活7d,37℃条件下放置1d病毒完全失活.

[目的]通过监测2018—2019年度上海市优势流行株A/H1N1(pdm09)亚型流感病毒对神经氨酸酶抑制剂(NAIs)的耐药情况,为上海市流感临床用药提供参考.[方法]随机选取60株A/H1N1(pdm09)亚型流行株,采用神经氨酸酶抑制实验及神经氨酸酶(NA)基因测序的方法,开展流行株对奥司他韦及扎那米韦敏感性和耐药性的监测和分析.[结果]60株流行株均对奥司他韦和扎那米韦敏感,未发现敏感性降低或者显著降低的情况;基因序列分析也未发现NA在催化活性关键位点及辅助位点出现氨基酸变异,佐证了神经氨酸酶抑制实验的表型检测结果.[结论]上海市2018—2019年度流行的A/H1N1(pdm09)亚型流感病毒对神经氨酸酶抑制剂依然敏感,为临床用药提供了科学参考.随着药物的广泛使用,应持续加强流感病毒耐药性监测,以有效指导临床用药.

Objective To observe the inactivation efficiency of photocataltic ceramics tile on influenza and poliomyelitis virus. Methods The inactivation efficiency of photocataltic ceramics tile on virus was detected by cell cultural and real-time PCR techniques. Results The inactivation logarithm values of influenza and poliomyelitis virus polluted on the photocataltic ceramics tile were 1. 66 TCID 50 and 0. 33 TCID 50 respectively after being under the fluorescent light for 4 hours. Those of influenza and poliomyelitis virus polluted on the photocataltic ceramics tile without lighting for 4 hours were 0. 15 TCID 50 and 0. 05 TCID 50 respectively. Conclusion The photocataltic ceramics tile can inactivate influenza and poliomyelitis viruses to some extent under fluorescent light,but can not damage the virus nucleic acid.