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Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research

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Abstract

HIV-1 infection causes injury to the central nervous system (CNS) and is often associated with neurocognitive disorders. One model for brain damage seen in AIDS patients is the transgenic (tg) mouse expressing a soluble envelope protein gp120 of HIV-1 LAV in the brain in astrocytes under the control of the promoter of glial fibrillary acidic protein. These GFAP-gp120tg mice manifest several key neuropathological features observed in AIDS brains, such as decreased synaptic and dendritic density, increased numbers of activated microglia, and pronounced astrocytosis. Several recent studies show that brains of GFAP-gp120tg mice and neurocognitively impaired HIV patients share also a significant number of differentially regulated genes, activation of innate immunity and other cellular signaling pathways, disturbed neurogenesis, and learning deficits. These findings support the continued relevance of the GFAP-gp120tg mouse as a useful model to investigate neurodegenerative mechanisms and develop therapeutic strategies to mitigate the consequences associated with HIV infection of the CNS, neuroAIDS, and HAND.

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Acknowledgements

This work was supported by NIH grants R01 MH087332, MH104131, and MH105330 (to M.K.) and P50 DA026306 (project 1 to A.M. and J.W.Y.; project 5 to M.K.). JAF was supported by R01 MH105319 (PI: Dr. C.L. Achim).

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Authors and Affiliations

  1. Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Victoria E. Thaney, Ana B. Sanchez, Ricky Maung & Marcus Kaul

  2. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    Jerel A. Fields, Arpi Minassian, Jared W. Young & Marcus Kaul

  3. Division of Biomedical Sciences, School of Medicine, University of California, Riverside, 900 University Ave, Riverside, CA, 92521, USA

    Marcus Kaul

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  1. Victoria E. Thaney
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Correspondence to Marcus Kaul.

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Thaney, V.E., Sanchez, A.B., Fields, J.A. et al. Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research. J. Neurovirol. 24, 156–167 (2018). https://doi.org/10.1007/s13365-017-0584-2

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