Induction of disseminated Mycobacterium avium in simian AIDS is dependent upon simian immunodeficiency virus strain and defective granuloma formation

Mycobacterium avium complex (MAC) is the most common disseminated bacterial disease in patients infected by the human immunodeficiency virus. Although murine models of disseminated MAC exist, they are primarily based on under lying genetic susceptibilities and cannot adequately address the complex in teractions that occur between host, mycobacteria, and immunosuppressive len tivirus. To address this problem we have developed an experimental system t o co-inoculate rhesus macaques with the simian immunodeficiency virus (SIV) and a clinical M. avium, isolate that results in a disease virtually ident ical to that observed in human cases. Using this experimental system we hav e found that the development of disseminated MAC is dependent on viral stra in. Animals co-infected with SIVmac251 and M. avium developed progressive d isease, whereas control animals and animals inoculated with closely related viruses (SIVmac239 and SIVmac239MER) developed self-limiting infections. T he ability of animals infected with SIVmac239 or SIVmac239MER to eliminate mycobacterial disease was independent of viral load and CD4 T-cell number b ut was correlated with the size and composition of microgranulomas. This wo rk establishes a novel primate model of disseminated MAC in the context of immunosuppressive lentiviral infection and advances our understanding of wh y human immunodeficiency virus-infected patients are remarkably sensitive t o the development of mycobacterial disease.