Immuno-Pharmacological Targeting of Virus-Containing Compartments in HIV-1-Infected Macrophages. Issue 7 (July 2016)

• Record Type: Journal Article
• Authors: Graziano, Francesca; Vicenzi, Elisa; Poli, Guido
• Is Part Of: Trends in microbiology. Volume 24:Issue 7(2016)
• Page Start: 558
• Page End: 567
• Publication Date: 2016-07
• Subjects: HIV (human immunodeficiency virus) -- macrophages -- VCC (virus-containing compartment) -- ATP -- microvesicles -- P2X7; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2016.02.018
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : In addition to CD4 T lymphocytes, HIV-1 infects tissue macrophages that can actively accumulate infectious virions in vacuolar subcellular structures mostly connected to the plasma membrane and recently termed virus-containing compartments (VCCs). The VCC-associated HIV-1 reservoir of infected macrophages can be either increased or depleted by immunologic and pharmacologic agents, at least in vitro, thus suggesting that these factors (or related molecules) could be effective in curtailing the macrophage-associated HIV-1 reservoir in infected individuals receiving combination antiretroviral therapy (cART). Here we review evidence on the pathogenic role of tissue macrophages as long-term viral reservoirs in vivo and upon in vitro infection with a particular emphasis on the immuno-pharmacological modulation of VCCs. Trends: HIV infects both CD4 T cells and myeloid cells, particularly tissue macrophages, via interaction with the primary receptor CD4 and a chemokine coreceptor, usually CCR5, but also CXCR4. Macrophage infection is characterized by a lack of gross cytopathicity, virus production for several weeks in culture, and accumulation of newly synthesized virions in pre-existing subcellular compartments named virus-containing compartments (VCCs). VCCs are usually connected to the plasma membrane and likely represent its profound invaginations. Several factors favor the accumulation of virions in VCCs; extracellular ATP, via interaction with P2X7, triggers the rapid release of virions from VCCs without inducing cell death. Imipramine, an antidepressant agent known to prevent the synthesis and release of ectosomes/microvesicles, counteracts ATP-dependent virion release from VCCs.