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Principal Investigator: Theresa L Chang
Organization: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
Fiscal Year: 2024
Award: $235,500
Funding agency: National Institute of Dental and Craniofacial Research
PROJECT SUMMARY
Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2), has been a major challenge for public health since the first case was reported in December
2019. In May 2023, the WHO and CDC marked the end of the COVID-19 public health emergency. However,
COVID-19 remains a threat due to continuously evolving new variants, and fully vaccinated people remain
susceptible to infection by the newer variants of the virus. SARS-CoV-2 entry is primarily mediated by binding
of the SARS-CoV-2 spike protein (receptor-binding domain, RBD) to the human angiotensin-converting
enzyme 2 (ACE2) receptor. Although ACE2-expressing cells support robust SARS-CoV-2 viral replication,
ACE2 expression profiles are not completely associated with clinical manifestations or immune responses.
Furthermore, SARS-CoV-2 infects organs or cells that do not express ACE2, suggesting the involvement of
alternative receptors for SARS-CoV-2. Our and other laboratories have identified ACE2-independent
alternative receptors for SARS-CoV-2, and infection via alternative receptors (e.g. CD147) is resistant to
monoclonal antibodies against spike RBD, which is the target for several SARS-CoV-2 vaccines to block ACE2
binding. Our preliminary data show that oral epithelial, salivary gland, and gingival epithelial cells are
susceptible to the replication-competent SARS-CoV-2 and pseudotyped SARS-CoV-2 Omicron variant
despite low or undetectable expression of ACE2. These oral epithelial cells do however express high levels of
alternative receptors CD147 or AXL, suggesting the role of alternative receptors in SARS-CoV-2 infection of
oral epithelial cells. We hypothesize that these alternative receptors play a critical role in SARS-CoV-2 infection
and virus-mediated immune activation in region-specific oral epithelial cells. In Aim 1, we will determine
repertories of receptors for SARS-CoV-2 and infection profiles in region-specific oral epithelial cells and tissues
from healthy subjects and subjects with oral inflammation pre- and post-treatment. In Aim 2, we will determine
the contribution of specific receptors to SARS-CoV-2 infection and virus-mediated immune activation in oral
epithelial cells. Considering that the virus will continue to infect humans regularly, it is critical to understand the
role of alternative receptors for SARS-CoV-2 in the oral mucosa, the potential portal of SARS-CoV-2 entry, to
develop anti-viral therapeutics and strategies to dampen virus-mediated immune activation and disease
outcomes, especially as regards emerging variants.
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structure><Organ><Play><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Predisposition><Prevent infection><Preventative strategy><Prevention strategy><Preventive strategy><Proteins><Public Health><RNA><RNA Gene Products><Receptor Protein><Reporting><Research><Resistance><Ribonucleic Acid><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.1.529><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 infection><SARS-CoV-2 omicron><SARS-CoV-2 omicron variant><SARS-CoV-2 pathogenesis><SARS-CoV-2 predisposition><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 susceptibility><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 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