Induction of an AIDS virus-related tuberculosis-like disease in macaques: a model of simian immunodeficiency virus- mycobacterium coinfection.
The mechanism by which human immunodeficiency virus (HIV)-Mycobacterium tuberculosis coinfection facilitates development of HIV-related tuberculosis is poorly characterized. Macaque models of simian immunodeficiency virus (SIV(mac))-Mycobacterium bovis BCG coinfection were employed to explore the pathogenesis of AIDS virus-related tuberculosis. Following BCG coinfection, SIV (SIV)-infected macaques with high viral loads developed an SIV-related tuberculosis-like disease. This disease was characterized clinically by a syndrome of diarrhea, anorexia, weight loss, and altered levels of consciousness and pathologically by the presence of disseminated granulomas. In contrast, SIV(mac)-infected macaques with low viral loads either showed no evidence of BCG-induced disease or developed focal granulomatous lesions. Pathogenic SIV-BCG interactions appeared to play a critical role in triggering the development of this SIV-related tuberculosis-like disease. BCG coinfection enhanced the destruction of CD4(+) T cells in SIV(mac)-infected macaques whose viral loads were high. Reciprocally, exacerbations of SIV disease led to marked suppression of BCG-specific T-cell responses, persistence of the BCG infection, and development of an SIV-related tuberculosis-like disease. Furthermore, development of this SIV-related tuberculosis-like disease was also seen in naïve macaques simultaneously inoculated with SIV(mac) and BCG. These results provide in vivo evidence that coinfection of AIDS virus-infected individuals with an avirulent mycobacterium can lead to development of a tuberculosis-like disease.
Shen
Yun
Y
Tuberculosis Research Unit, Beth Israel Deaconess Center. Harvard Medical School, Boston, Massachusetts 02215, USA.
Zhou
Dejiang
D
Chalifoux
Laura
L
Shen
Ling
L
Simon
Meredith
M
Zeng
Xuejun
X
Lai
Xioamin
X
Li
Yunyuan
Y
Sehgal
Prabhat
P
Letvin
Norman L
NL
Chen
Zheng W
ZW
D000163:Acquired Immunodeficiency Syndrome; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018450:Disease Progression; D006678:HIV; D006801:Humans; D008253:Macaca mulatta; D008254:Macaca nemestrina; D009163:Mycobacterium bovis / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013997:Time Factors; D014376:Tuberculosis / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology