Infectious Diseases and Immunity
Division of Basic and Translational Sciences
We are seeking Concept Clearance for a Request for Applications (RFA) that will encourage studies to examine the structure, biology, genetics, physiology and biochemistry of the oral mucosa and to compare these features with other mucosal surfaces, especially vaginal and rectal mucosa, in regard to susceptibility or resistance to HIV infection and replication.
Compared with the risks of becoming infected with HIV through unprotected rectal/vaginal intercourse, professional needle-stick injury, or IV drug injection, the relative risk of adults becoming infected through the oral route appears to be relatively low. Understanding this resistance in the oral cavity may suggest novel methods to prevent or diminish HIV infection at other mucosal sites. The oral mucosa differs from other mucosal surfaces in that it is generally thicker, composed of both keratinizing and non-keratinizing stratified squamous epithelial cells, and bathed in saliva. Oral epithelial cells are rich sources of microbicidal agents and innate host immune factors. Yet how the oral mucosa resists HIV infection while serving as a portal for many other types of viruses such as Epstein-Barr virus or human papillomavirus is undetermined and requires further research
Thus far, only a few studies suggest that oral epithelial cells may be infected with and harbor HIV. HIV provirus has been found in the epithelial tissues of HIV-infected individuals, although evidence of a productive infection is limited. HIV may gain access to target cells via epithelial cell transcytosis or through direct infection from the apical mucosal surface. HIV infection of subsets of epithelial cells, inhibition of spread of infectious virions throughout the epithelium and prevention of a productive HIV infection remain to be determined. Research is also needed on how the oral mucosa interacts with lymphocytes to produce a robust local immune response against HIV.
The oral mucosal surface is highly amenable to research; it is a readily accessible tissue and established sampling and experimental techniques are currently available. Few studies are examining the importance of these tissues in the potential prevention of HIV infection and AIDS-related oral manifestations. In particular, more research is needed on the uniqueness of the oral mucosa, compared to other mucosal surfaces such as vaginal or anal tissues, in HIV infection. We anticipate that this initiative will stimulate additional research in defining the immunological, genetic, physiological and biochemical aspects of the oral epithelium that confer susceptibility or resistance to HIV infections