Decoding Human Coronaviruses: Insights from Single-Cell RNA Sequencing in the Oral Cavity


The advent of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in late 2019 heralded a global health crisis, unfolding into the pandemic known as Coronavirus Disease 2019 (COVID-19). Characterized by its transmission through droplets, aerosols, and contaminated surfaces, SARS-CoV-2 became the seventh member of the human coronaviruses (HCoVs) family, joining the ranks of HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU1, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) .

Among these, SARS-CoV, MERS-CoV, and SARS-CoV-2 stand out for their high pathogenicity, exhibiting severe clinical manifestations, including fever, cough, and dyspnea, which can escalate to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and death, especially in older adults with comorbidities .

Mortality and Clinical Manifestations of HCoVs

The mortality rates associated with these viruses are notably disparate: 9.6% for SARS-CoV, 34.4% for MERS-CoV, and approximately 3.5% for SARS-CoV-2 . The less pathogenic coronaviruses, namely HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1, typically cause mild respiratory symptoms in immunocompetent individuals, suggesting a nuanced spectrum of virulence across the HCoV family .

SARS-CoV-2 and Oral Manifestations

Recent research has illuminated the occurrence of oral symptoms, such as dysgeusia, xerostomia, and oral mucosal lesions, as indicators of COVID-19, offering insights into the virus’s behavior within the oral cavity . Unlike its counterparts, SARS-CoV-2 has been notably detected in oral tissues, hinting at a potential role in viral transmission and pathogenesis within the oral ecosystem .

Cell Entry Mechanisms of Coronaviruses

The entry of coronaviruses into host cells is a complex process, involving the viral spike (S) protein and host receptors. SARS-CoV-2, SARS-CoV, and MERS-CoV utilize both cell surface and endosomal entry pathways. The angiotensin-converting enzyme 2 (ACE2) is a critical receptor for SARS-CoV and SARS-CoV-2, while dipeptidyl peptidase 4 (DPP4) facilitates MERS-CoV entry . Other HCoVs exhibit preferences for specific entry pathways, with HCoV-NL63 notably using ACE2 and clathrin-mediated endocytosis .

Viral Proteases and Host Factors

The role of proteases like TMPRSS2 and cathepsins in the viral entry process, and the identification of alternative receptors such as Basigin (BSG), underscore the complexity of HCoV-host interactions . Host cellular factors and restriction elements further influence the viral life cycle and pathogenic potential .

Oral Tropism and Viral Factors in the Oral Cavity

The oral manifestations of COVID-19 have spurred investigations into the oral tropism of coronaviruses, necessitating a deeper understanding of the relevant viral and cellular factors. Singh et al.’s profiling of SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell transcriptomics has paved the way for analyzing the presence and role of these factors in various oral tissues . Our study extends this work by examining additional viral factors, shedding light on the potential vulnerability of oral tissues to HCoV infections and the implications for disease transmission and pathogenesis.

In conclusion, the intricate interplay between human coronaviruses and their host cells, particularly in the context of oral health, highlights the necessity for comprehensive research to elucidate these mechanisms. This understanding is crucial for developing effective therapeutic interventions and managing the oral health implications of COVID-19 and other HCoV infections.

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