Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), JM Street, Parel, Mumbai, 400012, India.
MGM Institute of Health Sciences, MGM Educational Campus, Sector 1, Kamothe, Navi Mumbai, 410209, India.
J Assist Reprod Genet. 2021 Jul;38(7):1709-1720. doi: 10.1007/s10815-021-02192-3. Epub 2021 Apr 28.
To predict if developing human embryos are permissive to multiple coronaviruses.
We analyzed publicly available single-cell RNA-seq datasets of human embryos for the known canonical and non-canonical receptors and spike protein cleavage enzymes for multiple coronaviruses like SARS-CoV, SARS-CoV-2, MERS-CoV, hCoV-229E, and hCoV-NL63. We also analyzed the expression of host genes involved in viral replication, host proteins involved in viral endosomal sorting complexes required for transport (ESCRT), genes of host proteins that physically interact with proteins of SARS-CoV-2, and the host genes essential for coronavirus infectivity.
Of the known receptors of SARS viruses, ACE2, BSG, GOLGA7, and ZDHHC5 were expressed in different proportions in the zygote, 4-cell, 8-cell, morula, and blastocysts including the trophectoderm. The MERS-CoV receptor, DPP4, and hCoV-229E receptor, ANPEP, were expressed mainly from the compact morula to the blastocyst stages. Transcripts of the MERS-CoV alternate receptor LGALS1 were detected in most cells at all stages of development. TMPRSS2 transcripts were detected in the epiblast, primitive endoderm, and trophectoderm, while transcripts of the endosomal proteases CTSL, CTSB, and FURIN were expressed in most cells at all stages of development. ACE2 and TMPRSS2 were co-expressed in a proportion of epiblast and trophectoderm cells. The embryonic cells expressed genes involved in ESCRT, viral replication, SARS-CoV-2 interactions, and coronavirus infectivity. The ACE2 and TMPRSS2 co-expressing cells were enriched in genes associated with lipid metabolism, lysosome, peroxisome, and oxidative phosphorylation pathways.
Preimplantation and implantation stage human embryos could be permissive to multiple hCoVs.
预测人类胚胎是否允许多种冠状病毒感染。
我们分析了公共单细胞 RNA-seq 数据集，以确定人类胚胎中已知的冠状病毒的典型和非典型受体以及刺突蛋白切割酶，包括 SARS-CoV、SARS-CoV-2、MERS-CoV、hCoV-229E 和 hCoV-NL63。我们还分析了参与病毒复制的宿主基因、参与病毒内体分选复合物必需的运输（ESCRT）的宿主蛋白、与 SARS-CoV-2 蛋白物理相互作用的宿主蛋白基因以及冠状病毒感染必需的宿主基因的表达。
SARS 病毒的已知受体 ACE2、BSG、GOLGA7 和 ZDHHC5 在受精卵、4 细胞、8 细胞、桑葚胚和囊胚（包括滋养外胚层）中以不同的比例表达。MERS-CoV 受体 DPP4 和 hCoV-229E 受体 ANPEP 主要在致密桑葚胚到囊胚阶段表达。MERS-CoV 替代受体 LGALS1 的转录本在发育的各个阶段的大多数细胞中都被检测到。TMPRSS2 的转录本在上胚层、原始内胚层和滋养外胚层中被检测到，而内体蛋白酶 CTSL、CTSB 和 FURIN 的转录本在发育的各个阶段的大多数细胞中都被表达。ACE2 和 TMPRSS2 在一部分上胚层和滋养外胚层细胞中共同表达。胚胎细胞表达参与 ESCRT、病毒复制、SARS-CoV-2 相互作用和冠状病毒感染的基因。ACE2 和 TMPRSS2 共表达的细胞富集了与脂质代谢、溶酶体、过氧化物酶体和氧化磷酸化途径相关的基因。
着床前和着床期的人类胚胎可能允许多种 hCoVs 感染。
