Approximately 50% of AIDS patients have some evidence of ventricular dysfunction on echocardiography, while up to 20% develop symptoms due to an advanced dilated cardiomyopathy. Rhesus monkeys infected with the simian immunodeficiency virus (SIV) develop an immunodeficiency syndrome to AIDS in humans. Preliminary echocardiographic data generated by collaborators of Dr. Smith at the New England Primate Center indicate that about half of SIV-infected animals also develop evidence of ventricular dysfunction at 1 year. In this proposal, cohorts of animals newly infected with either virulent SIV or a non-virulent nef-delete SIV strain will be followed by serial echocardiograms, serologically to document immune system dysfunction, and clinically for evidence of opportunistic infection and ventricular dysfunction. At post-mortem, cardiac specimens will be prepared from SIV-infected and control animals for routine immunohistochemical analysis as well as for in situ hybridization and in situ PCR analysis for SIV, and for evidence of opportunistic infections such as CMV. Specimens will also be examined for evidence of cytokine- inducible nitric oxide synthase (NOS2) activation in cardiac myocytes, infiltrating inflammatory cells, and in the microvasculature. These data will provide important insights regarding the pathogenesis of AIDS-related cardiomyopathy in humans.
