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Neurovirulent Simian Immunodeficiency Virus Infection Induces Neuronal, Endothelial, and Glial Apoptosis

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Abstract

Background

Studies of human immunodeficiency virus type 1 (HIV-1) associated dementia have shown neuronal loss in discrete areas. The presence and mechanism of neuronal death, however, has remained quite elusive. One mechanism of cell death, apoptosis, has been clearly demonstrated outside the central nervous system (CNS) in HIV-1 infection but has not been firmly established within the CNS. Therefore, we set out to ascertain whether neuronal cell loss in simian immunodeficiency virus (SIV) encephalitis, an animal model of HIV-1–associated dementia, is a result of apoptosis.

Materials and Methods

With the aid of an in situ technique for identifying the 3′-OH ends of newly fragmented DNA characteristic of apoptosis, in conjunction with specific detected morphological criteria via light microscopy, we have examined encephalitic and nonencephalitic brains of macaques infected with a neurovirulent, neuroendotheliotropic strain of SIV to see if virus is spatially associated with apoptosis of neurons and nonneuronal cell types.

Results

We demonstrate the presence of DNA damage, indicative of apoptosis, in neurons, endothelial cells, and glial cells of the CNS of SIV-infected macaques. Furthermore, we observe an association between the localization of cells with significant DNA fragmentation and perivascular inflammatory cell infiltrates containing SIV-infected macrophages and multinucleated giant cells. Quantitative analysis reveals significantly more cells with DNA fragmentation in the CNS of macaques infected with neurovirulent, neuroendotheliotropic SIV strains as compared with strictly lymphocyte-tropic SIV strains and SIV negative controls.

Conclusions

Our findings of apoptosis in SIV-infected CNS may potentially lead to a better understanding of the AIDS dementia complex, ultimately providing a basis for better treatments.

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Acknowledgments

DCA is supported by USPHS NINDS Training Grant NS 07392; MCZ and JEC are supported by USPHS NINDS SIV Program Grant P01 NS 32208 and NS 35334; TMD is supported by USPHS NS 22643; and VLD is supported by USPHS NS 22643 and the American Federation for AIDS Research.

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Authors and Affiliations

  1. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    D. Cory Adamson, Ted M. Dawson & Valina L. Dawson

  2. Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street/Pathology 2-210, Baltimore, Maryland, 21287, USA

    D. Cory Adamson, Ted M. Dawson & Valina L. Dawson

  3. Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    M. Christine Zink & Janice E. Clements

  4. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Valina L. Dawson

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  1. D. Cory Adamson
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Adamson, D.C., Dawson, T.M., Zink, M.C. et al. Neurovirulent Simian Immunodeficiency Virus Infection Induces Neuronal, Endothelial, and Glial Apoptosis. Mol Med 2, 417–428 (1996). https://doi.org/10.1007/BF03401901

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