CD4-INDEPENDENT, CCR5-DEPENDENT INFECTION OF BRAIN CAPILLARY ENDOTHELIAL-CELLS BY A NEUROVIRULENT SIMIAN IMMUNODEFICIENCY VIRUS-STRAIN

Brain capillary endothelial cells (BCECs) are targets of CD4-independe nt infection by HIV-1 and simian immunodeficiency virus (SIV) strains in vitro and in vivo. Infection of BCECs may provide a portal of entry for the virus into the central nervous system and could disrupt blood -brain barrier function, contributing to the development of AIDS demen tia. We found that rhesus macaque BCECs express chemokine receptors in volved in HIV and SIV entry including CCR5, CCR3, CXCR4, and STRL33, b ut not CCR2b, GPR1, or GPR15. Infection of BCECs by the neurovirulent strain SIV/17E-Fr was completely inhibited by aminooxypentane regulati on upon activation, normal T cell expression and secretion in the pres ence or absence of ligands, but not by eotaxin or antibodies to CD4. W e found that the envelope (env) proteins from SIV/17E-Fr and several a dditional SIV strains mediated cell-cell fusion and virus infection wi th CD4-negative, CCR5-positive cells. In contrast, fusion with cells e xpressing the coreceptors STRL33, GPR1, and GPR15 was CD4-dependent. T hese results show that CCR5 can serve as a primary receptor for SIV in BCECs and suggest a possible CD4-independent mechanism for blood-brai n barrier disruption and viral entry into the central nervous system.