Downregulation of CCR5 on brain perivascular macrophages in simian immunodeficiency virus-infected rhesus macaques.

Background: C-C chemokine receptor 5 (CCR5) is a major coreceptor for Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) cell entry; however, its role in brain pathogenesis is largely understudied. Thus, we sought to examine cell type-specific protein expression of CCR5 during SIV infection of the brain.

Methods: We examined occipital cortical tissue from uninfected rhesus macaques and SIV-infected animals with or without encephalitis using immunohistochemistry and immunofluorescence microscopy to determine the number and distribution of CCR5-positive cells.

Lack of susceptibility in neonatally infected rhesus macaques to simian immunodeficiency virus-induced encephalitis.

Despite combination antiretroviral therapies making HIV a chronic rather than terminal condition for many people, the prevalence of HIV-associated neurocognitive disorders (HAND) is increasing. This is especially problematic for children living with HIV. Children diagnosed HAND rarely display the hallmark pathology of HIV encephalitis in adults, namely infected macrophages and multinucleated giant cells in the brain.

Overexpression and activation of colony-stimulating factor 1 receptor in the SIV/macaque model of HIV infection and neuroHIV.

In the present study, we investigated whether colony-stimulating factor 1 receptor (CSF1R) is expressed on brain macrophages and microglia in the human and macaque brain and whether it is upregulated and activated after lentivirus infection in vivo and contributes to development of encephalitic lesions. We examined, using multi-label and semi-quantitative immunofluorescence microscopy, the protein expression level and cellular localization of CSF1R in brain tissues from uninfected controls and SIV-infected adult macaques with or without encephalitis and also from uninfected controls, HIV-infected encephalitic subjects and virally suppressed subjects. In the normal uninfected brain, CSF1R protein was detected only on microglia and brain macrophages but not on neurons, astrocytes or oligodendrocytes.