We have shown that astrocytes in the brain are an important reservoir for HIV and that cell to cell contact with lymphocytes is necessary for viral entry and the lysosomal pathway in these cells regulates the intracellular trafficking of the virus and its ultimate ability to successfully infect these cells. Further, we have shown that the HIV protein Tat and the env protein of endogenous retrovirus-K are neurotoxic and we are now the underlying mechanisms involved in these effects. Finally, we have also discovered that the Tat protein of HIV can stimulate T cells in a T cell receptor independent manner using a unique mechanism. These activated T cells cause neuronal injury via the release of granzyme B that acts on cell receptors causing a cascade of events leading to neuronal dysfunction.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2011
Total Cost
$3,580,058
Indirect Cost
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State
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Johnson, Tory P; Nath, Avindra (2018) Neurological syndromes driven by postinfectious processes or unrecognized persistent infections. Curr Opin Neurol 31:318-324
Enose-Akahata, Yoshimi; Azodi, Shila; Smith, Bryan R et al. (2018) Immunophenotypic characterization of CSF B cells in virus-associated neuroinflammatory diseases. PLoS Pathog 14:e1007042
Sacktor, Ned; Skolasky, Richard L; Moxley, Richard et al. (2018) Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial. J Neurovirol 24:16-27
Nath, Avindra (2018) Association of Herpes Viral Infections, Antiherpetic Therapy, and Dementia: Real or Alternative Fact? Neurotherapeutics 15:415-416
Bowen, Lauren; Nath, Avindra; Smith, Bryan (2018) CNS immune reconstitution inflammatory syndrome. Handb Clin Neurol 152:167-176
Küry, Patrick; Nath, Avindra; Créange, Alain et al. (2018) Human Endogenous Retroviruses in Neurological Diseases. Trends Mol Med 24:379-394
Billioux, Bridgette Jeanne; Nath, Avindra; Stavale, Eric J et al. (2017) Cerebrospinal Fluid Examination in Survivors of Ebola Virus Disease. JAMA Neurol :
Shirazi, Talia N; Summers, Angela C; Smith, Bryan R et al. (2017) Concordance Between Self-Report and Performance-Based Measures of Everyday Functioning in HIV-Associated Neurocognitive Disorders. AIDS Behav 21:2124-2134
Douville, Renée N; Nath, Avindra (2017) Human Endogenous Retrovirus-K and TDP-43 Expression Bridges ALS and HIV Neuropathology. Front Microbiol 8:1986
Lee, Paul R; Johnson, Tory P; Gnanapavan, Sharmilee et al. (2017) Protease-activated receptor-1 activation by granzyme B causes neurotoxicity that is augmented by interleukin-1?. J Neuroinflammation 14:131

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