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HIV-1-Infected Astrocytes and the Microglial Proteome

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Abstract

The human immunodeficiency virus (HIV) invades the central nervous system early after viral exposure but causes progressive cognitive, behavior, and motor impairments years later with the onset of immune deficiency. Although in the brain, HIV preferentially replicates productively in cells of mononuclear phagocyte (MP; blood borne macrophage and microglia), astrocytes also can be infected, at low and variable frequency, particularly in patients with encephalitis. Among their many functions, astrocytes network with microglia to provide the first line of defense against microbial infection; however, very little is known about astrocytes’ consequences on MP. Here, we addressed this question using co-culture systems of HIV-infected mouse astrocytes and microglia. Pseudotyped vesicular stomatis virus/HIV was used to circumvent the absence of viral receptors and ensure cell genotypic uniformity for studies of intercellular communication. The study demonstrated that infected astrocytes show modest changes in protein elements compared to uninfected cells. In contrast, infected astrocytes induce robust changes in the proteome of HIV-1-infected microglia. Accelerated cell death and redox proteins, among others, were produced in abundance. The observations confirmed the potential of astrocytes to influence the neuropathogenesis of HIV-1 infection by specifically altering the neurotoxic potential of infected microglia and regulating viral maturation.

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Acknowledgements

We thank Dr. Ron Cerny, Nebraska Center for Mass Spectrometry, University of Nebraska- Lincoln, for his support for LC/MS/MS protein identification. We thank James Talaska and Janice Taylor of the Confocal Laser Scanning Microscope Core Facility at the University of Nebraska Medical Center (UNMC) for providing assistance with confocal microscopy, Jayme Horning at UNMC for assisting with MALDI-TOF/TOF, and Dr. R. Lee Mosley and Robin Taylor at UNMC for outstanding editorial support and critical reading of the manuscript. This work was supported by the Frances and Louis Blumkin Foundation, the Community Neuroscience Pride of Nebraska Research Initiative, the Alan Baer Charitable Trust, and National Institutes of Health grants 5P01NS31492 and DA17618 (to D.J.V.) and 2R37 NS36126, 2R01 NS034239, P20RR15635, U54NS43011, P01MH64570, and P01 NS43985 (to H.E.G.)

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Correspondence to Howard E. Gendelman.

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Wang, T., Gong, N., Liu, J. et al. HIV-1-Infected Astrocytes and the Microglial Proteome. J Neuroimmune Pharmacol 3, 173–186 (2008). https://doi.org/10.1007/s11481-008-9110-x

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  • DOI: https://doi.org/10.1007/s11481-008-9110-x

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