Applying Novel Pathogen Discovery to the Investigation of Infectious Causes of Heart Disease in Cats
Principal Investigator: Laura Goodman
Co-PI: Jennifer Grenier, Kathleen Kelly
DESCRIPTION (provided by applicant):
The cause of feline endomyocarditis (EMC) and left-ventricular endomyocardial fibrosis (LVEF), pathologic correlates of "endomyocardial restrictive cardiomyopathy” (RCM), is unknown. Severe, extensive endocardial scar tissue involving the left ventricle of older adult cats likely represents chronic repair of previous endocardial insult. Acute, fatal endomyocardial inflammation, or endomyocarditis (EMC), occurs in young cats; age and shared lesion distribution suggests EMC is an earlier manifestation of LVEF. The frequent association of EMC with interstitial pneumonia indicates infection. Although targeted PCR testing for specific agents has failed to identify a causative agent, new capabilities in next-generation sequencing (NGS) and bioinformatics provide powerful, unbiased tools to discover the cause of EMC-LVEF. We hypothesize that EMC is caused by an infectious etiology that co-infects both heart and lung, or primarily infects the lung with endocardial inflammation secondary to mediators from pulmonary damage. Using prospective and retrospective molecular pathology-based studies, we propose an exploratory clinico-pathologic investigation of EMC-interstitial pneumonia syndrome using NGS to discover previously uncharacterized non-host nucleic acid signatures as candidate causal pathogens.