Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain

Huanyu Dou, Justin Morehead, Jennifer Bradley, Santhi Gorantla, Brent Ellison, Jeff Kingsley, Lynette M Smith, Wei Chao, Galina Bentsman, David J. Volsky, Howard Eliot Gendelman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The balance between astrocyte and microglia neuroprotection and neurotoxicity defines the tempo of neuronal dysfunction during HIV-1-associated dementia (HAD). Astrocytes maintain brain homeostasis and respond actively to brain damage by providing functional and nutritive neuronal support. In HAD, low-level, continuous infection of astrocytes occurs, but the functional consequences of this infection are poorly understood. To this end, human fetal astrocytes (HFA) and monocyte-derived macrophages (MDM) were infected with HIV-1DJV and HIV-1NL4-3 (neurotropic and lymphotropic strains respectively) and a pseudotyped Vesicular Stomatitis Virus (VSV/HIV-1NL4-3) prior to intracranial injection into the basal ganglia of severe combined immunodeficient mice. Neuropathological and immunohistochemical comparisons for inflammatory and neurotoxic activities were performed amongst the infected cell types at 7 or 14 days. HIV-1-infected MDM induced significant increases in Mac-1, glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, and proinflammatory cytokine RNA and/or protein expression when compared with HSV/HIV-1- and HIV-1-infected HFA and sham-operated mice. Levels of neuron-specific nuclear protein, microtubule-associated protein 2, and neurofilament antigens were reduced significantly in the brain regions injected with human MDM infected with HIV-1DJV or VSV/HIV-1. We conclude that HIV-1 infection of astrocytes leads to limited neurodegeneration, underscoring the early and active role of macrophage-driven neurotoxicity in disease.

Original languageEnglish (US)
Pages (from-to)81-93
Number of pages13
JournalGlia
Volume54
Issue number2
DOIs
StatePublished - Aug 1 2006

Fingerprint

Astrocytes
HIV-1
Brain
Macrophages
HIV
Dementia
Vesicular Stomatitis
Microtubule-Associated Proteins
SCID Mice
Intermediate Filaments
Glial Fibrillary Acidic Protein
Human Herpesvirus 1
Microglia
Nuclear Proteins
Infection
Basal Ganglia
HIV Infections
Homeostasis
RNA
Cytokines

Keywords

  • Astrocytes
  • HIV-1-associated dementia
  • Inflammatory
  • Macrophages
  • Neurotoxicity
  • Severe combined immunodeficient mice

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain. / Dou, Huanyu; Morehead, Justin; Bradley, Jennifer; Gorantla, Santhi; Ellison, Brent; Kingsley, Jeff; Smith, Lynette M; Chao, Wei; Bentsman, Galina; Volsky, David J.; Gendelman, Howard Eliot.

In: Glia, Vol. 54, No. 2, 01.08.2006, p. 81-93.

Research output: Contribution to journalArticle

Dou, H, Morehead, J, Bradley, J, Gorantla, S, Ellison, B, Kingsley, J, Smith, LM, Chao, W, Bentsman, G, Volsky, DJ & Gendelman, HE 2006, 'Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain', Glia, vol. 54, no. 2, pp. 81-93. https://doi.org/10.1002/glia.20358
Dou, Huanyu ; Morehead, Justin ; Bradley, Jennifer ; Gorantla, Santhi ; Ellison, Brent ; Kingsley, Jeff ; Smith, Lynette M ; Chao, Wei ; Bentsman, Galina ; Volsky, David J. ; Gendelman, Howard Eliot. / Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain. In: Glia. 2006 ; Vol. 54, No. 2. pp. 81-93.
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