Modulation of astrocyte proliferation by HIV-1: Differential effects in productively infected, uninfected, and Nef-expressing cells

Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection

“…We attribute this disparity to inefficient virus entry into the majority of astrocytes that bind HIV-1. The block at entry was indicated by i) different dynamics of HIV-GFP association with HFA and CD4-positive cells at 37°C as visualized by fluorescence imaging; ii) the similarity between GFP-Vpr tagged NL4-3 and entry-defective 517B viruses in their respective target cell associations by the same method; and iii) the demonstration at a single cell level that circumventing restricted HIV-1 entry by use of VSV-G pseudotyped virus permits efficient infection of HFA, as also shown by cell population analyses in our previous studies [33,34,66] and consistent with other reports [34,67,84,90]. The 517B construct of HIV-1 contains a mutation in the fusion domain of gp41 that incapacitates virus-cell fusion and virus entry [77].…”

“…The significance of these overt astroglial pathologies is unknown but overall, unlike neurons, astrocytes rarely die in HIV-1-infected brains [31,32]. Productive infection of human astrocytes with HIV-1 has significant effects on cell physiology in vitro [33,34] and it associates with measurable neuropathology in a mouse model [35], suggesting that infected astrocytes, although infrequent, can have localized pathogenic effects.…”

Astrocyte Indoleamine 2,3-Dioxygenase Is Induced by the TLR3 Ligand Poly(I:C): Mechanism of Induction and Role in Antiviral Response

“…Chimeric HIV type 1 was generated by cotransfection of 293 T cells with pVSVg-env and pNL4-3 and added to astrocyte cultures at ϳ50 ng/ml of input p24. The chimera expressing the vesicular stomatitis virus G protein and HIV env (VSV-G HIV chimera) results in a high incidence of astrocyte infection, as previously described (13,65). VSVg-env HIV was also generated by cotransfecting 293 T cells with pVSVg-env and Envdeficient pNL4-3 obtained from Maurizio Federico, Istituto Superiore di Sanità, Rome, Italy (23).…”

Tissue-Specific HIV-1 Infection: Why it Matters

“…Virus replication and assembly in macrophages can diverge from what is observed in CD4 + T cells, with unintegrated HIV DNA serving as a source of transcription factors such as Tat and altering HIV replication [28]; the involvement of membrane-bound vacuoles in virus processing [54,56]; and replication enhancement by environmental nerve growth factor [57]. Latent HIV infection of the abundant and functionally diverse astrocytes, as defined by the presence of HIV DNA within these cells, occurs rather infrequently, and the clinical relevance of this cellular reservoir is unclear since HIV infection of astrocytes is reportedly not productive in vivo [58-64]. It is apparent that HIV exposure alters astrocyte function, contributes to neuropathogenesis and promotes neurotropism via the induction of chemokines (MCP-1, IL-10, IL-6, nitric oxide) [65-67].…”