Figure 2.

Schematic model of infection of monocytes and macrophages. A) Hypothetical ways to infect monocytes. Mo precursors may be infected before leaving the bone marrow (1) and then migrate to peripheral tissues where they differentiate into Mφ (2). Viral replication will then be reactivated leading to viral production and infection of neighboring cells (3). Alternatively, Mo subsets may become permissive to infection after being activated in the bone marrow or in the blood, owing to the inflammatory environment (4). Mos may be infected after encountering the virus or infected cells in inflamed tissues (5), where they then differentiate to Mφ. However, infected Mos might also transmigrate back to the blood (6). A Mo subset expressing CD16 that displays pro-inflammatory characteristics appears to be preferentially infected by HIV-1. B) Dissemination and control of HIV-1 infection in tissue macrophages. Infected Mos migrate to peripheral tissues such as brain, lungs and gastrointestinal tract where they differentiate and disseminate infection to resident microglial cells, alveolar Mφ or mucosal Mφ. The CD16+ subset has an enhanced capacity to transmigrate into tissues. Various factors that may control HIV-1 replication are present in peripheral compartments. Mφ from the mucosa of the gastrointestinal tract, where exposure to LPS is frequent, do not express CCR5 and are resistant to HIV-1 infection. An increased expression of the inhibitory C/EBPβ may suppress viral transcription in Mφ in brain and lungs, contributing to viral latency. Transcriptional silencing of the HIV-1 LTR by CTIP2 may contribute to HIV-1 latency in the CNS. uPA is also involved in the control of HIV-1 replication in the CNS and is sequestered by the soluble receptor suPAR in CNS disease.