Mycobacterium bovis bacille Calmette-Guerin enhances pathogenicity of simian immunodeficiency virus infection and accelerates progression to AIDS in macaques: A role of persistent T cell activation in AIDS pathogenesis

It has recently been proposed that Mycobacterium tuberculosis may enhance t he pathogenicity of HIV infections and accelerate the course of HIV disease , This hypothesis has been tested in the present study using a simian immun odeficiency virus of macaques (SIVmac)/Mycobacterium bovis bacille Calmette -Guerin (BCG)-coinfected macaque model. Naive and chronically SIVmac-infect ed monkeys were evaluated, Following BCG inoculation, the SIVmac-infected m onkeys exhibited the dominant responses of TCR-beta complementarity-determi ning region 3-restricted T cell subpopulations, This BCG-driven T cell acti vation correlated with a marked increase in viral loads in SIVmac-infected monkeys. Moreover, the prolonged T cell activation coincided,vith the enhan ced decline of CD4(+) PBL counts and the accelerated progression to clinica l AIDS in the coinfected monkeys, suggesting that Mycobacterium-driven T ce ll activation may be the mechanism underlying the enhanced pathogenicity of AIDS virus infection in the coinfected individuals. Within 2 to 7 mo after BCG coinfection, all chronically SIVmac-infected monkeys died from SIV-ind uced AIDS including tuberculosis-like disease, Surprisingly, the naive monk eys manifested a T cell activation-related toxic shock syndrome and a profo und depletion of CD4(+) lymphocytes 2 wk after simultaneous SIVmac/BCG inoc ulation. These naive animals died 2 mo after SIVmac/BCG inoculation, with t he evidence of the persistent SIV p27 antigenemia and SIVmac-induced diseas e. In contrast, the normal monkeys not infected with SIVmac survived BCG in fection; the control SIVmac-infected animals showed a natural course of chr onic SIV infection. Thus, results from this SIV/BCG coinfection model stron gly support the hypothesis that active coinfection with HIV and Mycobacteri um can impact remarkably on the AIDS virus-induced disease.