Abstract
BackgroundSARS-CoV-2, which has brought a huge negative impact on the world since the end of 2019, is reported to invade cells using the spike (S) protein to bind to angiotensin-converting enzyme II (ACE2) receptors on human cells while the transmembrane protease serine 2 (TMPRSS2) is the key protease that activates the S protein, which greatly facilitates the entry of SARS-CoV-2 into target cells. In our previous study, it was observed that the positive rate of SARS-CoV-2 nucleic acids in saliva was higher in male and the elderly COVID-19 patients, suggesting that the susceptibility of oral tissues to SARS-CoV-2 may be related to gender and age. This research aimed to further investigate the SARS-CoV-2 susceptibility in oral tissues and influencing factors from the perspective of ACE2 and TMPRSS2, which were two proteins closely associated with SARS-CoV-2 infection.MethodsImmunofluorescence was used to find the localization of ACE2 and TMPRSS2 in oral mucosal tissues. Transcriptomic sequencing data of several datasets were then collected to analysis the relationship between the expressions of ACE2 and TMPRSS2 with the age and gender of patients. Furthermore, oral tissues from patients with different ages and genders were collected. Immunohistochemistry staining, qRT-PCR and western blot were performed to explore the relationship between expression levels of ACE2 and TMPRSS2 and patient age as well as gender.ResultsThe results showed that the two proteins were able to be co-expressed in the epithelial cells of oral tissues, and their expression levels were higher in the relatively elderly group than those in relatively younger group. Male oral epithelial cells exhibited higher level of TMPRSS2.ConclusionsOur findings comprehensively confirmed the existence of ACE2 and TMPRSS2 in oral tissues and clarify the relationship between the expression levels with human age and gender for the first time, providing evidence for possible entry routes of SARS-CoV-2 and the influencing factors of SARS-CoV-2 colonization in oral cavity. Thus, the oral mucosa might be at potential risk of infection by SARS-CoV-2, especially in male or elderly patients. Using saliva to detect the nucleic acids of SARS-CoV-2 may be more accurate for elder male COVID-19 patients.
Highlights
SARS-CoV-2, which has brought a huge negative impact on the world since the end of 2019, is reported to invade cells using the spike (S) protein to bind to angiotensin-converting enzyme II (ACE2) receptors on human cells while the transmembrane protease serine 2 (TMPRSS2) is the key protease that activates the S protein, which greatly facilitates the entry of SARS-CoV-2 into target cells
We have found that SARS-CoV-2 could be detected in saliva by collecting saliva from COVID-19 patients and dry mouth as well as amblygeustia could be considered as initial symptoms of SARS-CoV-2 infection [12], which means oral tissues are most likely an important entry route for SARSCoV-2, and the susceptibility of oral epithelial cells to SARS-CoV-2 may be related to the expression levels of angiotensin converting enzyme 2 (ACE2) and TMPRSS2
Co‐expression of ACE2 and TMPRSS2 in oral epithelial cells As oral epithelium acts as a barrier against external substance, presence of SARS-CoV-2 in saliva samples from diagnosed patients firstly led us to consider the susceptibility of oral epithelial cells to the virus
Summary
SARS-CoV-2, which has brought a huge negative impact on the world since the end of 2019, is reported to invade cells using the spike (S) protein to bind to angiotensin-converting enzyme II (ACE2) receptors on human cells while the transmembrane protease serine 2 (TMPRSS2) is the key protease that activates the S protein, which greatly facilitates the entry of SARS-CoV-2 into target cells. Subsequent studies confirmed that the transmembrane protease serine 2 (TMPRSS2) is used for S protein activation, strengthening the binding of SARS-CoV-2 and ACE2, and the invasion of SARS-CoV-2 can be blocked by TMPRSS2 inhibitor [7,8,9] These studies suggest that cells expressing ACE2 and TMPRSS2 may be more susceptible to SARS-CoV-2 infection. We have found that SARS-CoV-2 could be detected in saliva by collecting saliva from COVID-19 patients and dry mouth as well as amblygeustia could be considered as initial symptoms of SARS-CoV-2 infection [12], which means oral tissues are most likely an important entry route for SARSCoV-2, and the susceptibility of oral epithelial cells to SARS-CoV-2 may be related to the expression levels of ACE2 and TMPRSS2. Few articles have focused on the differences in SARS-CoV-2 susceptibility of oral epithelial cells in different human groups
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