Antia Avan, Alvarado David M, Zeng Qiru, Casorla-Perez Luis A, Davis Deanna L, Sonnek Naomi M, Ciorba Matthew A, Ding Siyuan
Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Inflammatory Bowel Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Viruses. 2024 Apr 19;16(4):634. doi: 10.3390/v16040634.
The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread and spike protein cleavage in the Omicron spike protein, possibly contributing to its lower infectious particle levels. The findings highlight the variant-specific replication differences in human colonoids, providing insights into the enteric tropism of Omicron and its relevance to long COVID symptoms.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的奥密克戎变种，以包括BA.1、XBB.1.5、EG.5和JN.1在内的多个亚变种为特征，在2022年初成为主要毒株。研究表明，与原始毒株相比，奥密克戎在肺组织中的复制效率较低。然而，尽管70%的新冠患者会出现消化系统疾病症状，但奥密克戎在胃肠道中的传染性尚未完全明确。在此，我们使用原代人结肠类器官发现，尽管存在个体差异，但奥密克戎感染结肠细胞的情况与原始毒株或德尔塔变种相似，或效果更差。该变种诱导的III型干扰素表达有限，且对上皮完整性无显著影响。进一步实验揭示了奥密克戎刺突蛋白在细胞间传播效率低下以及刺突蛋白裂解情况，这可能导致其感染性颗粒水平较低。这些发现突出了人类结肠类器官中变种特异性的复制差异，为奥密克戎的肠道嗜性及其与新冠长期症状的相关性提供了见解。
