Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to humans.Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V...Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to humans.Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial cells.It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 did.After intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage.Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection.These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.展开更多
基金supported by the National Natural Science Foundation of China(81621005)。
文摘Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to humans.Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial cells.It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 did.After intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage.Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection.These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.
文摘本研究旨在观察血管紧张素转换酶Ⅱ(Angiotensin Converting EnzymeⅡ,ACE2)在CCl4中毒大鼠肝脏中的表达,并探讨其参与抗损伤的作用机制。16只120 g左右雄性SD大鼠随机分成对照组和试验组(n=8)。对照组大鼠腹腔注射生理盐水,试验组大鼠腹腔注射40%CCl4,首次剂量为5 mL.kg-1,以后每3 d 1次(剂量为3mL.kg-1),每周称重1次,4周后宰杀。测定平均日增体质量、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(Alb)、总蛋白(TP)、总胆红素(TBIL)、血浆血管紧张素Ⅱ(AngⅡ)含量、肝组织中ACE2含量和Mas受体mR-NA的表达及ACE2 mRNA的分布。结果表明:与对照组相比,试验组大鼠平均日增体质量、血清Alb和TP含量均显著下降(P<0.05),血清ALT和AST活性显著升高(P<0.05),血清TBIL和血浆AngⅡ含量没有显著性变化,Real-time PCR结果提示肝脏中ACE2和Mas受体的mRNA表达均显著上升(3.21±0.52 vs 1.03±0.11,P<0.01;1.64±0.22 vs 1.02±0.10,P<0.05),原位杂交结果显示对照组大鼠ACE2 mRNA着色较少,主要集中在中央静脉周围细胞,试验组大鼠ACE2大量出现在病变区域、胆管周围细胞、血管及微管内皮细胞当中。本研究表明CCl4诱导的肝损伤大鼠肝脏中ACE2和Mas受体的mRNA表达均增加,提示ACE2参与了肝脏的抗损伤过程,其机制可能是通过激活ACE2-Ang 1-7-Mas轴,减少AngⅡ的产生,从而减轻肝损伤。
