CHEMOKINE RECEPTOR EXPRESSION ON RESIDENT AND INFLAMMATORY CELLS IN THE BRAIN OF MACAQUES WITH SIMIAN IMMUNODEFICIENCY VIRUS ENCEPHALITIS

Although the mechanisms of human immunodeficiency virus (HIV) neuroinv asion, neuronal injury, and subsequent development of HIV-1-associated AIDS dementia complex are not fully understood, a correlation between monocyte/macrophage infiltrates in the brain and neurological disease exists. In light of the many potential roles that chemokines and chem okine receptors may play in HIV neuropathogenesis, we sought to descri be their pattern of expression in the SN-infected rhesus macaque model of HIV encephalitis. We previously demonstrated elevated expression o f the chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES, and interferon-inducible protein (IP)-10 in brain of mac aque monkeys with SIV encephalitis. In this study, we demonstrate that the corresponding chemokine receptors CCR3, CCR5, CXCR3, and CXCR4 ar e expressed in perivascular infiltrates in these same tissues. In addi tion, we detected CCR3, CCR5, and CXCR4 on subpopulations of large hip pocampal and neocortical pyramidal neurons and on glial cells in both normal and encephalitic brain. These findings suggest that multiple ch emokines and their receptors contribute to monocyte and lymphocyte rec ruitment to the brain in SIV encephalitis. Furthermore, the expression of known HIV/SIV co-receptors on neurons suggests a possible mechanis m whereby HIV or SIV can directly interact with these cells, disruptin g their normal physiological function and contributing to the pathogen esis of AIDS dementia complex.