Increase of C1q biosynthesis in brain microglia and macrophages during lentivirus infection in the rhesus macaque is sensitive to antiretroviral treatment with 6-chloro-2′,3′-dideoxyguanosine

Candan Depboylu; Martin K.-H. Schäfer; Wilhelm J. Schwaeble; Todd A. Reinhart; Hitomi Maeda; Hiroaki Mitsuya; Ruslan Damadzic; Dianne M. Rausch; Lee E. Eiden; Eberhard Weihe

Neurobiology of Disease (Oct 2005)

Increase of C1q biosynthesis in brain microglia and macrophages during lentivirus infection in the rhesus macaque is sensitive to antiretroviral treatment with 6-chloro-2′,3′-dideoxyguanosine

Candan Depboylu,
Martin K.-H. Schäfer,
Wilhelm J. Schwaeble,
Todd A. Reinhart,
Hitomi Maeda,
Hiroaki Mitsuya,
Ruslan Damadzic,
Dianne M. Rausch,
Lee E. Eiden,
Eberhard Weihe

Affiliations

Candan Depboylu: Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Robert-Koch-Str. 8, 35033 Marburg, Germany; Department of Neurology, Center for Nervous Diseases, Philipps University, Marburg, Germany
Martin K.-H. Schäfer: Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Robert-Koch-Str. 8, 35033 Marburg, Germany
Wilhelm J. Schwaeble: Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Robert-Koch-Str. 8, 35033 Marburg, Germany; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
Todd A. Reinhart: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Hitomi Maeda: Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Hiroaki Mitsuya: Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Ruslan Damadzic: Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA
Dianne M. Rausch: Division of Mental Disorders, Behavioral Research and AIDS, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA
Lee E. Eiden: Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA
Eberhard Weihe: Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Robert-Koch-Str. 8, 35033 Marburg, Germany; Corresponding author. Fax: +49 6421 2868965.

Journal volume & issue: Vol. 20, no. 1
pp. 12 – 26

Abstract

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Complement activation in the brain contributes to the pathology of neuroinflammatory and neurodegenerative diseases such as neuro-AIDS. Using semiquantitative in situ hybridization and immunohistochemistry, we observed an early and sustained increase in the expression of C1q, the initial recognition subcomponent of the classical complement cascade, in the CNS during simian immunodeficiency virus (SIV) infection of rhesus macaques. Cells of the microglial/macrophage lineage were the sources for C1q protein and transcripts. C1q expression was observed in proliferating and infiltrating cells in SIV-encephalitic brains. All SIV-positive cells were also C1q-positive. Treatment with the CNS-permeant antiretroviral agent 6-chloro-2′,3′-dideoxyguanosine decreased C1q synthesis along with SIV burden and focal inflammatory reactions in the brains of AIDS-symptomatic monkeys. Thus, activation of the classical complement arm of innate immunity is an early event in neuro-AIDS and a possible target for intervention.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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