Cellular aspects of HIV-1 infection of macrophages leading to neuronal dysfunction in in vitro models for HIV-1 encephalitis.
HIV-1 is a hematogenously spread virus that most likely gains entry into the brain within blood-derived macrophages. Indeed, productive viral replication selectively occurs within perivascular and parenchymal blood-derived macrophages and microglia and HIV-infected macrophages have increased potential to bind and transmigrate through the blood-brain barrier. Once inside the brain, HIV-infected macrophages secrete a variety of pro-inflammatory mediators that display neuromodulatory and neurotoxic activities in several in vitro models for HIV-1 encephalitis. The final outcome regarding neuronal function and cell loss is regulated through intercellular interactions between these virus-infected cells and astrocytes. In this regard, both HIV-induced intracellular events in macrophages and interactions between HIV-infected macrophages and brain cells are reviewed as factors that might lead to neuronal injury in in vitro model systems for HIV-1 encephalitis.
Nottet
H S
HS
Eijkman-Winkler Institute, Section Neuroviroimmunology, Utrecht, The Netherlands.
Bär
D R
DR
van Hassel
H
H
Verhoef
J
J
Boven
L A
LA
D015526:AIDS Dementia Complex / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000821:virology; D001921:Brain / Q000503:physiopathology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D017628:Microglia / Q000821:virology; D008954:Models, Biological; D009474:Neurons / Q000502:physiology* / Q000821:virology*; D014779:Virus Replication