Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) can invade the central nervous system (CNS) during acute infection but virus replication is apparently controlled because clinical and pathological manifestations of CNS disease in HIV/SIV-infected individuals usually present later in infection, coincident with immunosuppression and acquired immunodeficiency syndrome (AIDS). Using an established SIV/macaque model of HIV dementia, the authors recently demonstrated that acute virus replication is down-regulated (to undetectable viral RNA levels) in the brain, but not the periphery, as early as 21 days post inoculation (p.i.). Viral DNA levels in the brain remain constant, suggesting that infected cells persist in the CNS and that replication is inhibited largely at a transcriptional level. In vitro, active replication of HIV in macrophages can be inhibited by treatment with interferon (IFN)β via a mechanism involving induction of a dominant-negative form of the transcription factor C/EBP (CCAAT/enhancer-binding protein)β. Because macrophages are the primary cell types infected with HIV/SIV in the CNS and HIV replication in macrophages requires C/EBP sites within the viral long terminal repeat (LTR), the authors considered the possibility that suppression of C/EBP-dependent transcription contributes to the mechanism by which acute HIV/SIV replication is inhibited in the CNS. Here, the authors report that IFNβ can also inhibit ongoing SIV replication in macaque macrophages in vitro. Further, the authors demonstrate that IFNβ levels in the brain increase between 7 and 21 days p.i. in parallel with increased expression of the dominant-negative isoform of C/EBPβ. These results suggest that innate immune responses involving IFNβ may contribute to the mechanism(s) controlling acute SIV replication in the CNS.
- CCAAT/enhancer-binding protein (C/EBP)β
- Dominant-negative C/EBPβ
- Interferon (IFN)β
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience