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Persistent EcoHIV infection induces nigral degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice

Abstract

The widespread use of antiretroviral therapy for treatment of human immunodeficiency virus (HIV) infections has dramatically improved the quality and duration of life for HIV-positive individuals. Despite this success, HIV persists for the life of an infected person in tissue reservoirs including the nervous system. Thus, whether HIV exacerbates age-related brain disorders such as Parkinson’s disease (PD) is of concern. In support of this idea, HIV infection can be associated with motor and gait abnormalities that parallel late-stage manifestations of PD including dopaminergic neuronal loss. With these findings in hand, we investigated whether viral infection could affect nigrostriatal degeneration or exacerbate chemically induced nigral degeneration. We now demonstrate an additive effect of EcoHIV on dopaminergic neuronal loss and neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. HIV-1-infected humanized mice failed to recapitulate these EcoHIV results suggesting species-specific neural signaling. The results demonstrate a previously undefined EcoHIV-associated neurodegenerative response that may be used to model pathobiological aspects of PD.

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Acknowledgements

We thank the University of Nebraska Medical Center Flow Cytometry Core Research Facility for the flow cytometric data acquisition and technical support and Dr. Rebecca Wilshusen and Dr. Charles Schutt for their assistance with the mouse studies. We wish to thank Dr. Eran Hadas for the preparation of the EcoHIV used in these studies. This work was supported in part by NIH Grants AG043540, DA028555, NS036126, NS034239, MH064570, NS043985, and MH062261; DOD Grant 421-20-09A; and the Carol Swarts Emerging Neuroscience Fund to HEG, MH086372, MH083627, DA017618, DA037611, MH104145, DA037611 (DJV), MH104145 (DJV and HEG), and NS094146 (MJP).

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Correspondence to Howard E. Gendelman.

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Olson, K.E., Bade, A.N., Namminga, K.L. et al. Persistent EcoHIV infection induces nigral degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice. J. Neurovirol. 24, 398–410 (2018). https://doi.org/10.1007/s13365-018-0629-1

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Keywords

  • Parkinson’s disease
  • Central nervous system
  • EcoHIV
  • Human immunodeficiency virus
  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine