NATURAL CONTROL OF M AVIUM IN SAIDS

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The objectives of this pilot project are to establish the source of Mycobacterium avium infection in SIV-infected monkeys, characterize immune correlates of disease, and determine the feasibility of vaccination to prevent opportunistic infection of SAIDS animals with M. avium. The incidence of M. avium infection (MAI) in the SAIDS colony has increased from undetectable levels in 1988 to 18-25% in recent years. This opportunistic infection produces diarrhea, cachexia, and sometimes pneumonia in severely immunocompromized monkeys with remarkable similarity to MAI in children with AIDS. We detect M. avium by culture and PCR and characterize isolates from the environment (soil and water) and monkeys by molecular fingerprint analysis. To date, isolates from the environment rarely infect deep tissues of monkeys. In vitro testing of monkey macrophages demonstrates that cells co-infected with SIV and a common strain of pathogenic M. avium found in our monkey colony produces higher than expecte d levels of virus. Protein components of our pathogenic strain are being characterized. We have demonstrated that animals infected with SIV and severely immunodeficient can be infected with our pathogenic strain (MavK128) while inoculation with a human strain of M. avium (Serovar 4) fails to infect immunodeficient monkeys. In a pilot study vaccination of four animals with sonicated M. avium prior to SIV-infection failed to protect them from challenge with MavK128 but lesions contained more lymphocytes than expected. Future studies could look for promising formulations of M. avium and adjuvant that might provide protection against opportunistic infection. FUNDING Venture Research PUBLICATIONS Greenberg SS, Xie JM, Kolls J, Mason C, Didier P. Rapid induction of mRNA for nitric oxide synthase II in rat alveolar macrophages by intratracheal administration of Mycobacterium tuberculosis and Mycobacterium avium. Proc Soc Exp Bio Med, 209:46-53, 1995. Didier P, Ramesh G, Newman G, Maslow J. Detection of M. avium by PCR in rhesus monkeys. [Abstract #2486]. FASEB J, 10(6):A1431, 1996. Brar I, Didier P, Murphey-Corb M, Newman GW, Maslow JN. Prevalence of Mycobacterium avium complex (MAC) infection in SIV infected monkeys. [Abstract]. Infectious Diseases Society Meeting, September 1996, New Orleans, LA. Brar I, Didier P, Murphey-Corb M, Maslow JN. Epidemiology of Mycobacterium avium complex (MAC) infection in simian immunodeficiency virus (SIV) infected rhesus monkeys. [Abstract #655], p185, 4th Conference on Retroviruses and Opportunistic Infections, Washington, DC, January 22-26, 1997.