Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIANS003130-01
Application #
8367141
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2011
Total Cost
$3,580,058
Indirect Cost

  Institution

Name
National Institute of Neurological Disorders and Stroke
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
Tyagi, Richa; Li, Wenxue; Parades, Danelvis et al. (2017) Inhibition of human endogenous retrovirus-K by antiretroviral drugs. Retrovirology 14:21
Hategan, Alina; Bianchet, Mario A; Steiner, Joseph et al. (2017) HIV Tat protein and amyloid-? peptide form multifibrillar structures that cause neurotoxicity. Nat Struct Mol Biol 24:379-386
Abrams, Rachel P M; Solis, Jamie; Nath, Avindra (2017) Therapeutic Approaches for Zika Virus Infection of the Nervous System. Neurotherapeutics 14:1027-1048
Wiznitzer, Max; Nath, Avindra (2017) Acute flaccid myelitis and enterovirus D68: Déjà vu all over again. Neurology 89:112-113

Showing the most recent 10 out of 87 publications