This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS), together, lead to the death of more than four million people annually, world-wide. New drugs and vaccines are urgently needed to combat both the TB and AIDS. Robust animal models of TB, AIDS and TB-AIDS co-infection will be a crucial part of the strategy to develop and test vaccines and drugs against these diseases. It has been possible to model AIDS extremely well in rhesus macaques infected with Simian immune Virus (SIV). These macaques undergo a rapid decline in the CD4+ T cell levels in peripheral blood and various lymphoid tissues following infection, and develop chronic to acute AIDS characterized by severe immune deficiency. We have recently demonstrated the capability to infect rhesus macaques with a high- or low-dose of aerosolized (Mycobacterium tuberculosis) Mtb, producing active pulmonary TB and latent disease, respectively. Thus, infection of macaques with Mtb accurately recapitulates the host-driven diversity of human TB. We have recently shown that while a high-dose infection with Mtb produces acute TB, low-dose infection with Mtb produces asymptomatic, latent infection in rhesus. We now show that co-infection with 300 TCID50 SIVmac239 can rapidly reactivate latent TB into acute TB. This is accompanied by significantly reduced survival of co-infected animals, higher bacillary burden and granulomatous lesion involvement in lung as well as disseminated disease in extra-thoracic tissues such as spleen, liver and kidney.
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