Ebraham Laith, Xu Chuan, Wang Annie, Hernandez Cyril, Siclari Nicholas, Rajah Divino, Walter Lewins, Marras Salvatore A E, Tyagi Sanjay, Fine Daniel H, Daep Carlo Amorin, Chang Theresa L
Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
Global Technology Center, Colgate-Palmolive Company, Piscataway, NJ 08855, USA.
Pathogens. 2023 Jun 19;12(6):843. doi: 10.3390/pathogens12060843.
The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication-competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Distinct viral dynamics were seen in hTERT TIGKs compared to A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells on day 3 after infection. Analysis of oral epithelial cells infected by replication-competent SARS-CoV-2 viruses expressing GFP showed that the GFP signal and SARS-CoV-2 mRNAs were not evenly distributed. Furthermore, we found cumulative SARS-CoV-2 RNAs from released viruses in the media from oral epithelial cells on day 1 and day 2 after infection, indicating productive viral infection. Taken together, our results demonstrated that oral epithelial cells were susceptible to SARS-CoV-2 viruses despite low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for the development of future vaccines and therapeutics.
口腔被认为是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）进入人体的门户之一，尽管SARS-CoV-2病毒活跃口腔感染的证据有限。我们评估了SARS-CoV-2在口腔上皮细胞中感染和复制的能力。用具有复制能力的SARS-CoV-2病毒和表达SARS-CoV-2刺突蛋白的假型病毒对占据口腔不同区域的口腔牙龈上皮细胞（hTERT TIGKs）、唾液腺上皮细胞（A-253）和口腔颊上皮细胞（TR146）进行攻击。所有表达不可检测或低水平人类血管紧张素转换酶2（hACE2）但高水平替代受体CD147的口腔上皮细胞都易受SARS-CoV-2感染。与A-253和TR146细胞相比，hTERT TIGKs中观察到了不同的病毒动态。例如，感染后第3天，hTERT TIGKs中的病毒转录本水平持续存在，但在A-253和TR146细胞中显著下降。对感染表达绿色荧光蛋白（GFP）的具有复制能力的SARS-CoV-2病毒的口腔上皮细胞进行分析表明，GFP信号和SARS-CoV-2 mRNA分布不均。此外，我们发现感染后第1天和第2天口腔上皮细胞培养基中释放病毒的累积SARS-CoV-2 RNA，表明病毒感染具有生产性。综上所述，我们的结果表明，尽管hACE2水平低或不可检测，口腔上皮细胞仍易受SARS-CoV-2病毒感染，这表明替代受体有助于SARS-CoV-2感染，可能被用于未来疫苗和治疗方法的开发。
