CHEMOKINE RECEPTOR EXPRESSION IN BRAIN OF MACAQUES W/ SIV ENCEPHALITIS

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Although the mechanisms of HIV neuroinvasion, neuronal injury, and subsequent development of HIV-1-associated AIDS dementia complex (ADC) are not fully understood, a correlation between monocyte/macrophage infiltrates in the brain and neurologic disease exists In light of the many potential roles that chemokines and chemokine receptors may play in HIV neuropathogenesis, we sought to describe their pattern of expression in the SIV-infected rhesus macaque model of HIV encephalitis We previously demonstrated elevated expression of the chemokines MIP-1`, MIP-1 , RANTES, and IP-10 in brain of macaque monkeys with SIV encephalitis In this study, we demonstrate that the corresponding chemokine receptors CCR3, CCR5, CXCR3 and also CXCR4 are expressed in perivascular infiltrates in these same tissues In addition, we detected CCR3, CCR5, and CXCR4 on subpopulations of large hippocampal and neocortical pyramidal neurons and on glial cells in both normal and encephaliti c b rain These findings suggest that multiple chemokines and their receptors contribute to monocyte and lymphocyte recruitment to the brain in SIV encephalitis Furthermore, the expression of known HIV/SIV coreceptors on neurons suggests a possible mechanism whereby HIV or SIV can directly interact with these cells, disrupting their normal physiologic function and contributing to the pathogenesis of ADC Publications Westmoreland SV, Rottman JB, Williams KC, Lackner AA, Sasseville VG Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with SIV encephalitis Am J Pathol, 152:659-665, 1998