Viral infection and antiviral immunity in the oral cavity

Individual tissues have distinct antiviral properties garnered through various mechanisms, including physical characteristics, tissue-resident immune cells and commensal organisms. Although the oral mucosa has long been appreciated as a critical barrier tissue that is exposed to a continuous barrage of pathogens, many fundamental aspects of the antiviral immune response in this tissue remain unknown. Several viral pathogens, such as herpesviruses and human papillomaviruses, have been acknowledged both historically and at present for infections in the oral cavity that result in substantial clinical burden. However, recent viral outbreaks, including those with SARS-CoV-2 and mpox, featured oral symptoms even though these viruses are not generally considered oral pathogens. Ensuing studies have shown that the oral cavity is an important locale for viral infection and potential transmission of newly emergent or re-emergent pathogens, highlighting the need for an increased understanding of the mechanisms of antiviral immunity at this site. In this Review, we provide a broad overview of antiviral immune responses in the oral cavity and discuss common viral infections and their manifestations in the oral mucosa. In addition, we present current mouse models for the study of oral viral infections.