Comparison of the effects of pathogenic simian human immunodeficiency virus strains SHIV-89.6P and SHIV-KU2 in cynomolgus macaques.
Factors explaining why human immunodeficiency virus (HIV) enhances the risk of reactivated tuberculosis (TB) are poorly understood. Unfortunately, experimental models of HIV-induced reactivated TB are lacking. We examined whether cynomolgus macaques, which accurately model latent TB in humans, could be used to model pathogenesis of HIV infection in the lungs and associated lymph nodes. These experiments precede studies modeling the effects of HIV infection on latent TB. We infected two groups of macaques with chimeric simian-human immunodeficiency viruses (SHIV-89.6P and SHIV-KU2) and followed viral titers and immunologic parameters including lymphocytes numbers and phenotype in the blood, bronchoalveolar lavage cells, and lymph nodes over the course of infection. Tissues from the lungs, liver, kidney, spleen, and lymph nodes were similarly examined at necropsy. Both strains produced dramatic CD4(+) T cell depletion. Plasma titers were not different between viruses, but we found more SHIV-89.6P in the lungs. Both viruses induced similar patterns of cell activation markers. SHIV-89.6P induced more IFN-gamma expression than SHIV-KU2. These results indicate SHIV-89.6P and SHIV-KU2 infect cynomolgus macaques and may be used to accurately model effects of HIV infection on latent TB.
Pawar
Santosh N
SN
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Mattila
Joshua T
JT
Sturgeon
Timothy J
TJ
Lin
Philana Ling
PL
Narayan
Opendra
O
Montelaro
Ronald C
RC
Flynn
Joanne L
JL
D000818:Animals; D018893:Bronchoalveolar Lavage; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006678:HIV / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000821:virology; D008252:Macaca fascicularis; D016865:Reassortant Viruses / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
D007371:Interferon-gamma