Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis

• Published in: The American journal of pathology Vol. 152; no. 3; pp. 659 - 665
• Main Authors: Westmoreland, SV, Rottman, JB, Williams, KC, Lackner, AA, Sasseville, VG
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01-03-1998; American Society for Investigative Pathology
• Subjects: AIDS/HIV; Animals; Biological and medical sciences; Brain - metabolism; Brain - pathology; Brain - virology; Chemokines - metabolism; Encephalitis, Viral - etiology; Encephalitis, Viral - metabolism; Encephalitis, Viral - pathology; Human viral diseases; Immunohistochemistry; Infectious diseases; Macaca mulatta; Medical sciences; Receptors, Chemokine - metabolism; Simian Acquired Immunodeficiency Syndrome - etiology; Simian Acquired Immunodeficiency Syndrome - metabolism; Simian Acquired Immunodeficiency Syndrome - pathology; Simian Immunodeficiency Virus; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Immunohistochemistry; Pathogenesis; Monkey; Infiltrate; Primates; Biological receptor; Immunopathology; Encephalitis; Nervous system diseases; Retroviridae; AIDS; Immune deficiency; Lentivirus; Cerebral disorder; Infection; Virus; Chemokine; Pathology; Vertebrata; Experimental disease; Mammalia; Viral disease; Animal; Central nervous system disease; Inflammatory cell; Simian immunodeficiency virus
• ISSN: 0002-9440; 1525-2191

Although the mechanisms of human immunodeficiency virus (HIV) neuroinvasion, 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 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 macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, and interferon-inducible protein (IP)-10 in brain of macaque monkeys with SIV encephalitis. In this study, we demonstrate that the corresponding chemokine receptors CCR3, CCR5, CXCR3, and 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 encephalitic brain. 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 co-receptors on neurons suggests a possible mechanism whereby HIV or SIV can directly interact with these cells, disrupting their normal physiological function and contributing to the pathogenesis of AIDS dementia complex.