Abstract
Despite the inability of HIV-1 to infect neurons, over half of the HIV-1-infected population in the USA suffers from neurocognitive dysfunction. HIV-infected immune cells in the periphery enter the central nervous system by causing a breach in the blood–brain barrier. The damage to the neurons is mediated by viral and host toxic products released by activated and infected immune and glial cells. To evaluate the toxicity of any viral isolate, viral protein, or host inflammatory protein, we describe a protocol to assess the neuronal apoptosis and synaptic compromise in primary cultures of human neurons and astrocytes.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSpringer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group C, Group H (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16. doi:10.1007/s13365-010-0006-1
Resnick L, Berger JR, Shapshak P, Tourtellotte WW (1988) Early penetration of the blood-brain-barrier by HIV. Neurology 38:9–14
Airoldi M, Bandera A, Trabattoni D, Tagliabue B, Arosio B, Soria A, Rainone V, Lapadula G, Annoni G, Clerici M, Gori A (2012) Neurocognitive impairment in HIV-infected naïve patients with advanced disease: the role of virus and intrathecal immune activation. Clin Dev Immunol 2012:467154. doi:10.1155/2012/467154
An SF, Groves M, Gray F, Scaravilli F (1999) Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals. J Neuropathol Exp Neurol 58:1156–1162
Meltzer MS, Skillman DR, Gomatos PJ, Kalter DC, Gendelman HE (1990) Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol 8:169–194. doi:10.1146/annurev.iy.08.040190.001125
Toborek M, Lee YW, Flora G, Pu H, Andras IE, Wylegala E, Hennig B, Nath A (2005) Mechanisms of the blood-brain barrier disruption in HIV-1 infection. Cell Mol Neurobiol 25:181–199
Rao VR, Ruiz AP, Prasad VR (2014) Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND). AIDS Res Ther 11:13. doi:10.1186/1742-6405-11-13
Rao VR, Neogi U, Eugenin E, Prasad VR (2014) The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to Southern African HIV-1C isolates. PLoS One 9:e107074. doi:10.1371/journal.pone.0107074
Rao VR, Neogi U, Talboom JS, Padilla L, Rahman M, Fritz-French C, Gonzalez-Ramirez S, Verma A, Wood C, Ruprecht RM, Ranga U, Azim T, Joska J, Eugenin E, Shet A, Bimonte-Nelson H, Tyor WR, Prasad VR (2013) Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. Retrovirology 10:61. doi:10.1186/1742-4690-10-61
Acknowledgements
This work was supported by NIH R01 MH083579 and R21 MH101003 (to V.R.P.). The authors would like to thank Arthur Ruiz for critically reading the manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Rao, V.R., Eugenin, E.A., Prasad, V.R. (2016). Evaluating the Role of Viral Proteins in HIV-Mediated Neurotoxicity Using Primary Human Neuronal Cultures. In: Prasad, V., Kalpana, G. (eds) HIV Protocols. Methods in Molecular Biology, vol 1354. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3046-3_25
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3046-3_25
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3045-6
Online ISBN: 978-1-4939-3046-3
eBook Packages: Springer Protocols