Role of Feline Calicivirus Infection in Cats with Naturally-Occurring Feline Chronic Gingivostomatitis
Principal Investigator: Santiago Peralta
Co-PI: John S. Parker
DESCRIPTION (provided by applicant):
Feline chronic gingivostomatitis (FCGS) is a common disease of major clinical significance. Multiple studies have identified a positive correlation between isolation of feline calicivirus (FCV) and FCGS. However, the role of FCV in the disease is unclear and basic information regarding the distribution of viral mRNA and antigens in affected and normal oral tissues is unavailable. It is unknown if FCV replicates within the inflamed oral tissues. Establishing this basic knowledge will guide future therapeutic and investigative efforts.
We hypothesize that FCV infection is a causative factor in the pathogenesis of FCGS and plays a role in stimulating the chronic inflammatory response associated with disease. This hypothesis is based on the high prevalence of FCV in cats with FCGS, the nature of the chronic inflammatory response (predominantly lymphoplasmacytic infiltrate) which is consistent with a chronic viral infection, and the capacity of experimental FCV infection to induce acute gingivitis-stomatitis. We have 4 objectives: (i) Identify tissue sites and cells within the oral mucosa of cats with FCGS where FCV genome and viral antigens are present; (ii) Determine the distribution of the FCV receptor, feline Junctional Adhesion Molecule A (fJAM-A) in normal feline oral tissues and in those of animals with FCGS; (iii) Determine whether serially collected FCV isolates from cats with FCGS are different and compare the in vitro growth kinetics of isolates from cats with FCGS to other FCV isolates; and (iv) Perform metagenomic analysis to rule out other potential pathogens and confirm the presence of FCV.
We will use immunohistochemistry (IHC) and in situ hybridization (ISH) to assess the distribution of viral antigen, and RNA genome in tissues. The distribution of fJAM-A in tissues will be determined by IHC. We will use RNA-seq and plaque assays to assess strain similarities and the in vitro growth kinetics of viral isolates from cats with FCGS. Metagenomic analysis of sequences from samples will be determined by RNA-seq using swabs and/or biopsy samples collected from affected and control tissues. We expect to find FCV genome and antigen within inflamed tissues in cats with FCGS, as well as dysregulated expression of fJAM-A in affected tissues. The metagenomic analysis will provide detailed information regarding possible pathogens involved in the inflammatory response. We expect this analysis will confirm the presence of FCV and will perhaps uncover other pathogens that are commonly associated with the disease. Better understanding of the role FCV plays in this disease will allow new therapeutic strategies to be designed, provide justification for current therapies, and guide future studies.