Effect of human immunodeficiency virus on blood-brain barrier integrity and function: An update

Frontiers in Cellular Neuroscience

Volumn 9, Issue June, 2015, Pages 1-10

  Atluri, Venkata Subba Rao ^a   Hidalgo, Melissa ^a   Samikkannu, Thangavel ^a   Venkata Kurapati, Kesava Rao ^a   Jayant, Rahul Dev ^a   Sagar, Vidya ^a   Nair, Madhavan P N ^a  

^a FLORIDA INTERNATIONAL UNIVERSITY   (United States)

Author keywords

Blood brain barrier; Gp120; HIV; Nef; Neurocognitive disorders; Tat; Vpr

Indexed keywords

ANTIRETROVIRUS AGENT; GAG PROTEIN; GLYCOPROTEIN GP 120; NEF PROTEIN; POL PROTEIN; TRANSACTIVATOR PROTEIN; VIRUS ENVELOPE PROTEIN; VIRUS PROTEIN;

ARTICLE; ASTROCYTE; BLOOD BRAIN BARRIER; BLOOD VESSEL PERMEABILITY; BRAIN FUNCTION; CELL MEMBRANE PERMEABILITY; DISEASE COURSE; HIV ASSOCIATED DEMENTIA; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LATENT VIRUS INFECTION; MACROPHAGE; MICROGLIA; NANOMEDICINE; NONHUMAN;

EID: 84935827294     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2015.00212     Document Type: Article

References (97)

1. Abbott, N. J. (2002). Astrocyte-endothelial interactions and blood-brain barrier permeability. J. Anat. 200, 629-638. doi: 10.1046/j.1469-7580.2002.00064.x
2. Abraham, L., and Fackler, O. T. (2012). HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun. Signal. 10:39. doi: 10.1186/1478-811X-10-39
3. Acheampong, E. A., Parveen, Z., Muthoga, L. W., Kalayeh, M., Mukhtar, M., and Pomerantz, R. J. (2005). Human immunodeficiency virus type 1 Nef potently induces apoptosis in primary human brain microvascular endothelial cells via the activation of caspases. J. Virol. 79, 4257-4269. doi: 10.1128/jvi.79.7.4257- 4269.2005
4. Albini, A., Soldi, R., Giunciuclio, D., Girauo, E., Benelli, R., Primo, L., et al. (1996). The angiogenesis induced by HIV-1 Tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells. Nat. Med. 2, 1371-1375. doi: 10.1038/nm1296-1371
5. Anthony, I. C., Ramage, S. N., Carnie, F. W., Simmonds, P., and Bell, J. E. (2005). Influence of HAART on HIV-related CNS disease and neuroinflammation. J. Neuropathol. Exp. Neurol. 64, 529-536.
6. Argyris, E. G., Acheampong, E., Nunnari, G., Mukhtar, M., Williams, K. J., and Pomerantz, R. J. (2003). Human immunodeficiency virus type 1 enters primary human brain microvascular endothelial cells by a mechanism involving cell surface proteoglycans independent of lipid rafts. J. Virol. 77, 12140-12151. doi: 10.1128/jvi.77.22.12140-12151.2003
7. Ashraf, T., Jiang, W., Hoque, M., Henderson, J., Wu, C., and Bendayan, R. (2014). Role of anti-inflammatory compounds in human immunodeficiency virus-1 glycoprotein120-mediated brain inflammation. J. Neuroinflammation 11:91. doi: 10.1186/1742-2094-11-91
8. Atluri, V. S., Kanthikeel, S. P., Reddy, P. V., Yndart, A., and Nair, M. P. (2013). Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND). PLoS One 8:e61399. doi: 10.1371/journal.pone.0061399
9. Atluri, V. S., Pilakka-Kanthikeel, S., Samikkannu, T., Sagar, V., Kurapati, K. R., Saxena, S. K., et al. (2014). Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder. Mol. Brain 7:37. doi: 10.1186/1756-6606-7-37
10. Bagasra, O., Lavi, E., Bobroski, L., Khalili, K., Pestaner, J. P., Tawadros, R., et al. (1996). Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10, 573-585. doi: 10.1097/00002030-199606000-00002
11. Ballabh, P., Braun, A., and Nedergaard, M. (2004). The blood-brain barrier: an overview: structure, regulation and clinical implications. Neurobiol. Dis. 16, 1-13. doi: 10.1016/j.nbd.2003.12.016
12. Banks, W. A., Ortiz, L., Plotkin, S. R., and Kastin, A. J. (1991). Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism. J. Pharmacol. Exp. Ther. 259, 988-996.
13. Banks, W. A., Robinson, S. M., and Nath, A. (2005). Permeability of the blood- brain barrier to HIV-1 Tat. Exp. Neurol. 193, 218-227. doi: 10.1016/j.expneurol.2004.11.019
14. Bobardt, M. D., Salmon, P., Wang, L., Esko, J. D., Gabuzda, D., Fiala, M., et al. (2004). Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J. Virol. 78, 6567-6584. doi: 10.1128/jvi.78.12.6567-6584.2004
15. Boisselier, E., and Astruc, D. (2009). Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev. 38, 1759-1782. doi: 10.1039/b806051g
16. Churchill, M. J., Wesselingh, S. L., Cowley, D., Pardo, C. A., McArthur, J. C., Brew, B. J., et al. (2009). Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann. Neurol. 66, 253-258. doi: 10.1002/ana.21697
17. Cioni, C., and Annunziata, P. (2002). Circulating gp120 alters the blood-brain barrier permeability in HIV-1 gp120 transgenic mice. Neurosci. Lett. 330, 299-301. doi: 10.1016/s0304-3940(02)00814-5
18. Conant, K., Tornatore, C., Atwood, W., Meyers, K., Traub, R., and Major, E. O. (1994). In vivo and in vitro infection of the astrocyte by HIV-1. Adv. Neuroimmunol. 4, 287-289. doi: 10.1016/s0960-5428(06)80269-x
19. Cosenza, M. A., Zhao, M. L., Si, Q., and Lee, S. C. (2002). Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol. 12, 442-455. doi: 10.1111/j.1750- 3639.2002.tb00461.x
20. Dallasta, L. M., Pisarov, L. A., Esplen, J. E., Werley, J. V., Moses, A. V., Nelson, J. A., et al. (1999). Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Am. J. Pathol. 155, 1915-1927. doi: 10.1016/s0002-9440(10)65511-3
21. Danave, I. R., Tiffany-Castiglioni, E., Zenger, E., Barhoumi, R., Burghardt, R. C., and Collisson, E. W. (1994). Feline immunodeficiency virus decreases cell-cell communication and mitochondrial membrane potential. J. Virol. 68, 6745-6750.
22. Ding, H., Sagar, V., Agudelo, M., Pilakka-Kanthikeel, S., Atluri, V. S., Raymond, A., et al. (2014). Enhanced blood-brain barrier transmigration using a novel transferrin embedded fluorescent magneto-liposome nanoformulation. Nanotechnology 25:055101. doi: 10.1088/0957-4484/25/5/055101
23. Dohgu, S., Ryerse, J. S., Robinson, S. M., and Banks, W. A. (2012). Human immunodeficiency virus-1 uses the mannose-6-phosphate receptor to cross the blood-brain barrier. PLoS One 7:e39565. doi: 10.1371/journal.pone.0039565
24. Ellaurie, M., Calvelli, T. A., and Rubinstein, A. (1990). Human immunodeficiency virus (HIV) circulating immune complexes in infected children. AIDS Res. Hum. Retroviruses 6, 1437-1441. doi: 10.1089/aid.1990.6.1437
25. Eugenin, E. A., and Berman, J. W. (2007). Gap junctions mediate human immunodeficiency virus-bystander killing in astrocytes. J. Neurosci. 27, 12844-12850. doi: 10.1523/jneurosci.4154-07.2007
26. Eugenin, E. A., Clements, J. E., Zink, M. C., and Berman, J. W. (2011). Human immunodeficiency virus infection of human astrocytes disrupts blood-brain barrier integrity by a gap junction-dependent mechanism. J. Neurosci. 31, 9456-9465. doi: 10.1523/JNEUROSCI.1460-11.2011
27. Eugenin, E. A., Dyer, G., Calderon, T. M., and Berman, J. W. (2005). HIV- 1 tat protein induces a migratory phenotype in human fetal microglia by a CCL2 (MCP-1)-dependent mechanism: possible role in NeuroAIDS. Glia 49, 501-510. doi: 10.1002/glia.20137
28. Eugenin, E. A., Osiecki, K., Lopez, L., Goldstein, H., Calderon, T. M., and Berman, J. W. (2006). CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J. Neurosci. 26, 1098-1106. doi: 10.1523/jneurosci.3863-05.2006
29. Faccini, A. M., Cairney, M., Ashrafi, G. H., Finbow, M. E., Campo, M. S., and Pitts, J. D. (1996). The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts. J. Virol. 70, 9041-9045.
30. Ferrucci, A., Nonnemacher, M. R., and Wigdahl, B. (2013). Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival. J. Neurovirol. 19, 239-253. doi: 10.1007/s13365-013-0170-1
31. Frankel, A. D., and Young, J. A. (1998). HIV-1: fifteen proteins and an RNA. Annu. Rev. Biochem. 67, 1-25. doi: 10.1146/annurev.biochem.67.1.1
32. Goldstein, G. W. (1988). Endothelial cell-astrocyte interactions. A cellular model of the blood-brain barrier. Ann. N Y Acad. Sci. 529, 31-39. doi: 10.1111/j.1749-6632.1988.tb51417.x
33. González-Scarano, F., and Martín-García, J. (2005). The neuropathogenesis of AIDS. Nat. Rev. Immunol. 5, 69-81. doi: 10.1038/nri1527
34. Guduru, R., Liang, P., Runowicz, C., Nair, M., Atluri, V., and Khizroev, S. (2013). Magneto-electric nanoparticles to enable field-controlled high-specificity drug delivery to eradicate ovarian cancer cells. Sci. Rep. 3:2953. doi: 10.1038/srep02953
35. Gutierrez, E. G., Banks, W. A., and Kastin, A. J. (1993). Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J. Neuroimmunol. 47, 169-176. doi: 10.1016/0165-5728(93)90027-v
36. Hawkins, B. T., and Davis, T. P. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev 57, 173-185. doi: 10.1124/pr.57.2.4
37. Hayashi, Y., Nomura, M., Yamagishi, S. I., Harada, S. I., Yamashita, J., and Yamamoto, H. (1997). Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia 19, 13-26. doi: 10.1002/(sici)1098-1136(199701)19:1<13::aid-glia2>3.3.co;2-e
38. He, J., Choe, S., Walker, R., Di Marzio, P., Morgan, D. O., and Landau, N. R. (1995). Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J. Virol. 69, 6705-6711.
39. Heinzinger, N. K., Bukinsky, M. I., Haggerty, S. A., Ragland, A. M., Kewalramani, V., Lee, M. A., et al. (1994). The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc. Natl. Acad. Sci. U S A 91, 7311-7315. doi: 10.1073/pnas.91.15.7311
40. Huang, W., Eum, S. Y., András, I. E., Hennig, B., and Toborek, M. (2009). PPARalpha and PPARgamma attenuate HIV-induced dysregulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities. FASEB J. 23, 1596-1606. doi: 10.1096/fj.08-121624
41. Iadecola, C., and Nedergaard, M. (2007). Glial regulation of the cerebral microvasculature. Nat. Neurosci. 10, 1369-1376. doi: 10.1038/nn2003
42. Ivey, N. S., Renner, N. A., Moroney-Rasmussen, T., Mohan, M., Redmann, R. K., Didier, P. J., et al. (2009). Association of FAK activation with lentivirus-induced disruption of blood-brain barrier tight junction-associated ZO-1 protein organization. J. Neurovirol. 15, 312-323. doi: 10.1080/13550280902998413
43. Jayant, R. D., Atluri, V. S., Agudelo, M., Sagar, V., Kaushik, A., and Nair, M. (2015). Sustained-release nanoART formulation for the treatment of neuroAIDS. Int. J. Nanomedicine 10, 1077-1093. doi: 10.2147/IJN.s76517
44. Kanmogne, G. D., Primeaux, C., and Grammas, P. (2005). HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: implications for the pathogenesis of HIV-associated dementia. J. Neuropathol. Exp. Neurol. 64, 498-505.
45. Kanmogne, G. D., Schall, K., Leibhart, J., Knipe, B., Gendelman, H. E., and Persidsky, Y. (2007). HIV-1 gp120 compromises blood-brain barrier integrity and enhances monocyte migration across blood-brain barrier: implication for viral neuropathogenesis. J. Cereb. Blood Flow Metab. 27, 123-134. doi: 10.1038/sj.jcbfm.9600330
46. Khan, N. A., Di Cello, F., Nath, A., and Kim, K. S. (2003). Human immunodeficiency virus type 1 tat-mediated cytotoxicity of human brain microvascular endothelial cells. J. Neurovirol. 9, 584-593. doi: 10.1080/jnv.9.6.584.593
47. Kielian, T., and Esen, N. (2004). Effects of neuroinflammation on glia-glia gap junctional intercellular communication: a perspective. Neurochem. Int. 45, 429-436. doi: 10.1016/j.neuint.2003.09.010
48. Klein, R. S., Williams, K. C., Alvarez-Hernandez, X., Westmoreland, S., Force, T., Lackner, A. A., et al. (1999). Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. J. Immunol. 163, 1636-1646.
49. Knabb, M. T., Danielsen, C. A., McShane-Kay, K., Mbuy, G. K., and Woodruff, R. I. (2007). Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication. Virus Res. 124, 212-219. doi: 10.1016/j.virusres.2006.11.006
50. Letendre, S., Marquie-Beck, J., Capparelli, E., Best, B., Clifford, D., Collier, A. C., et al. (2008). Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch. Neurol. 65, 65-70. doi: 10.1001/archneurol.2007.31
51. Liu, Y., Jones, M., Hingtgen, C. M., Bu, G., Laribee, N., Tanzi, R. E., et al. (2000). Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat. Med. 6, 1380-1387. doi: 10.1038/82199
52. Louboutin, J. P., Agrawal, L., Reyes, B. A., Van Bockstaele, E. J., and Strayer, D. S. (2010). HIV-1 gp120-induced injury to the blood-brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress. J. Neuropathol. Exp. Neurol. 69, 801-816. doi: 10.1097/NEN.0b013e3181e8c96f
53. Louboutin, J.P., and Strayer, D. S. (2012). Blood-brain barrier abnormalities caused by HIV-1 gp120: mechanistic and therapeutic implications. ScientificWorld Journal 2012:482575. doi: 10.1100/2012/482575
54. Luabeya, M. K., Dallasta, L. M., Achim, C. L., Pauza, C. D., and Hamilton, R. L. (2000). Blood-brain barrier disruption in simian immunodeficiency virus encephalitis. Neuropathol. Appl. Neurobiol. 26, 454-462. doi: 10.1046/j.1365- 2990.2000.00275.x
55. Ma, J., Yuan, X., Qu, H., Zhang, J., Wang, D., Sun, X., et al. (2015). The role of reactive oxygen species in morphine addiction of SH-SY5Y cells. Life Sci. 124, 128-135. doi: 10.1016/j.lfs.2015.01.003
56. Mahajan, S. D., Aalinkeel, R., Law, W.-C., Reynolds, J. L., Nair, B. B., Sykes, D. E., et al. (2012). Anti-HIV-1 nanotherapeutics: promises and challenges for the future. Int. J. Nanomedicine 7, 5301-5314. doi: 10.2147/IJN.s25871
57. Mankowski, J. L., Spelman, J. P., Ressetar, H. G., Strandberg, J. D., Laterra, J., Carter, D. L., et al. (1994). Neurovirulent simian immunodeficiency virus replicates productively in endothelial cells of the central nervous system in vivo and in vitro. J. Virol. 68, 8202-8208.
58. McArthur, J. C., and Brew, B. J. (2010). HIV-associated neurocognitive disorders: is there a hidden epidemic? AIDS 24, 1367-1370. doi: 10.1097/QAD.0b013e3283391d56
59. Mishra, R., and Singh, S. K. (2014). HIV-1 Tat C phosphorylates VE-cadherin complex and increases human brain microvascular endothelial cell permeability. BMC Neurosci. 15:80. doi: 10.1186/1471-2202-15-80
60. Nakagawa, S., Castro, V., and Toborek, M. (2012). Infection of human pericytes by HIV-1 disrupts the integrity of the blood-brain barrier. J. Cell. Mol. Med. 16, 2950-2957. doi: 10.1111/j.1582-4934.2012.01622.x
61. Nakamuta, S., Endo, H., Higashi, Y., Kousaka, A., Yamada, H., Yano, M., et al. (2008). Human immunodeficiency virus type 1 gp120-mediated disruption of tight junction proteins by induction of proteasome-mediated degradation of zonula occludens-1 and -2 in human brain microvascular endothelial cells. J. Neurovirol. 14, 186-195. doi: 10.1080/135502808019 93630
62. Nowacek, A., and Gendelman, H. E. (2009). NanoART, neuroAIDS and CNS drug delivery. Nanomedicine (Lond.) 4, 557-574. doi: 10.2217/nnm.09.38
63. Nuovo, G. J., Gallery, F., MacConnell, P., and Braun, A. (1994). In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-alpha RNA in the central nervous system. Am. J. Pathol. 144, 659-666.
64. Ohagen, A., Ghosh, S., He, J., Huang, K., Chen, Y., Yuan, M., et al. (1999). Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope. J. Virol. 73, 897-906.
65. Orellana, J. A., Sáez, J. C., Bennett, M. V. L., Berman, J. W., Morgello, S., and Eugenin, E. A. (2014). HIV increased the release of dickkopf-1 (DKK1) protein from human astrocytes by a Cx43 hemichannel-dependent mechanism. J. Neurochem. 128, 752-763. doi: 10.1111/jnc.12492
66. Osmanov, S., Pattou, C., Walker, N., Schwardländer, B., Esparza, J., and WHO- UNAIDS Network for HIV Isolation and Characterization (2002). Estimated global distribution and regional spread of HIV-1 genetic subtypes in the year 2000. J. Acquir. Immune Defic. Syndr. 29, 184-190. doi: 10.1097/00042560-200202010-00013
67. Peluso, R., Haase, A., Stowring, L., Edwards, M., and Ventura, P. (1985). A Trojan horse mechanism for the spread of visna virus in monocytes. Virology 147, 231-236. doi: 10.1016/0042-6822(85)90246-6
68. Persidsky, Y., and Gendelman, H. E. (2003). Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J. Leukoc. Biol. 74, 691-701. doi: 10.1189/jlb.0503205
69. Persidsky, Y., Heilman, D., Haorah, J., Zelivyanskaya, M., Persidsky, R., Weber, G. A., et al. (2006). Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Blood 107, 4770-4780. doi: 10.1182/blood-2005-11-4721
70. Persidsky, Y., Stins, M., Way, D., Witte, M. H., Weinand, M., Kim, K. S., et al. (1997). A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis. J. Immunol. 158, 3499-3510.
71. Pilakka-Kanthikeel, S., Atluri, V. S., Sagar, V., Saxena, S. K., and Nair, M. (2013). Targeted Brain Derived Neurotropic Factors (BDNF) delivery across the blood-brain barrier for neuro-protection using magnetic nano carriers: an in-vitro study. PLoS One 8:e62241. doi: 10.1371/journal.pone.0062241
72. Price, T. O., Ercal, N., Nakaoke, R., and Banks, W. A. (2005). HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells. Brain Res. 1045, 57-63. doi: 10.1016/j.brainres.2005.03.031
73. Pu, H., Tian, J., Andras, I. E., Hayashi, K., Flora, G., Hennig, B., et al. (2005). HIV-1 Tat protein-induced alterations of ZO-1 expression are mediated by redox-regulated ERK 1/2 activation. J. Cereb. Blood Flow Metab. 25, 1325-1335. doi: 10.1038/sj.jcbfm.9600125
74. Ramirez, S. H., Haskó, J. N., Skuba, A., Fan, S., McCormick, R., Dykstra, H., et al. (2012). Activation of cannabioid receptor 2 attenuates leukocyte-endothelial interactions and blood-brain barrier dysfunction under inflammatory conditions. J. Neurosci. 32, 4004-4016. doi: 10.1523/JNEUROSCI.4628-11.2012
75. Risau, W. (1991). Induction of blood-brain barrier endothelial cell differentiation. Ann. N Y Acad. Sci. 633, 405-419. doi: 10.1111/j.1749-6632.1991.tb15630.x
76. Risau, W., and Wolburg, H. (1990). Development of the blood-brain barrier. Trends Neurosci. 13, 174-178. doi: 10.1016/0166-2236(90)90043-A
77. Rouach, N., Avignone, E., Même, W., Koulakoff, A., Venance, L., Blomstrand, F., et al. (2002). Gap junctions and connexin expression in the normal and pathological central nervous system. Biol. Cell 94, 457-475. doi: 10.1016/s0248- 4900(02)00016-3
78. Rubin, L. L., and Staddon, J. M. (1999). The cell biology of the blood-brain barrier. Annu. Rev. Neurosci. 22, 11-28. doi: 10.1146/annurev.neuro.22.1.11
79. Saez, J. C., Berthoud, V. M., Branes, M. C., Martinez, A. D., and Beyer, E. C. (2003). Plasma membrane channels formed by connexins: their regulation and functions. Physiol. Rev. 83, 1359-1400. doi: 10.1152/physrev.00007.2003
80. Sagar, V., Pilakka-Kanthikeel, S., Pottathil, R., Saxena, S. K., and Nair, M. (2014). Towards nanomedicines for neuro-AIDS. Rev. Med. Virol. 24, 103-124. doi: 10.1002/rmv.1778
81. Saiyed, Z. M., Gandhi, N. H., and Nair, M. P. (2010). Magnetic nanoformulation of azidothymidine 5′-triphosphate for targeted delivery across the blood-brain barrier. Int. J. Nanomedicine 5, 157-166. doi: 10.2147/IJN.S8905
82. Sansing, H. A., Renner, N. A., and Maclean, A. G. (2012). An inverted blood-brain barrier model that permits interactions between glia and inflammatory stimuli. J. Neurosci. Methods 207, 91-96. doi: 10.1016/j.jneumeth.2012.03.015
83. Sharma, D. P., Zink, M. C., Anderson, M., Adams, R., Clements, J. E., Joag, S. V., et al. (1992). Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaques. J. Virol. 66, 3550-3556.
84. Sporer, B., Koedel, U., Paul, R., Kohleisen, B., Erfle, V., Fontana, A., et al. (2000). Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9. J. Neuroimmunol. 102, 125-130. doi: 10.1016/s0165-5728(99)00170-8
85. Stevens, P. R., Gawryluk, J. W., Hui, L., Chen, X., and Geiger, J. D. (2014). Creatine protects against mitochondrial dysfunction associated with HIV- 1 Tat-induced neuronal injury. Curr. HIV Res. 12, 378-387. doi: 10.2174/1570162X13666150121101544
86. Stolp, B., Imle, A., Coelho, F. M., Hons, M., Gorina, R., Lyck, R., et al. (2012). HIV- 1 Nef interferes with T-lymphocyte circulation through confined environments in vivo. Proc. Natl. Acad. Sci. U S A 109, 18541-18546. doi: 10.1073/pnas.1204322109
87. Takahashi, K., Wesselingh, S. L., Griffin, D. E., McArthur, J. C., Johnson, R. T., and Glass, J. D. (1996). Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann. Neurol. 39, 705-711. doi: 10.1002/ana.410390606
88. Toborek, M., Lee, Y., Flora, G., Pu, H., András, I., Wylegala, E., et al. (2005). Mechanisms of the blood-brain barrier disruption in HIV-1 infection. Cell Mol. Neurobiol. 25, 181-199. doi: 10.1007/s10571-004-1383-x
89. Tornatore, C., Chandra, R., Berger, J. R., and Major, E. O. (1994). HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44, 481-487. doi: 10.1212/WNL.44.3_Part_1.481
90. Vanitharani, R., Mahalingam, S., Rafaeli, Y., Singh, S. P., Srinivasan, A., Weiner, D. B., et al. (2001). HIV-1 Vpr transactivates LTR-directed expression through sequences present within −278 to −176 and increases virus replication in vitro. Virology 289, 334-342. doi: 10.1006/viro.2001.1153
91. Vyas, T. K., Shah, L., and Amiji, M. M. (2006). Nanoparticulate drug carriers for delivery of HIV/AIDS therapy to viral reservoir sites. Expert Opin. Drug Deliv. 3, 613-628. doi: 10.1517/17425247.3.5.613
92. Weiss, N., Miller, F., Cazaubon, S., and Couraud, P.-O. (2009). The blood-brain barrier in brain homeostasis and neurological diseases. Biochim. Biophys. Acta 1788, 842-857. doi: 10.1016/j.bbamem.2008.10.022
93. Wiley, C. A., Schrier, R. D., Nelson, J. A., Lampert, P. W., and Oldstone, M. B. (1986). Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc. Natl. Acad. Sci. U S A 83, 7089-7093. doi: 10.1073/pnas.83.18.7089
94. Wong, H. L., Chattopadhyay, N., Wu, X. Y., and Bendayan, R. (2010). Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv. Drug Deliv. Rev. 62, 503-517. doi: 10.1016/j.addr.2009.11.020
95. Xu, R., Feng, X., Xie, X., Zhang, J., Wu, D., and Xu, L. (2012). HIV-1 Tat protein increases the permeability of brain endothelial cells by both inhibiting occludin expression and cleaving occludin via matrix metalloproteinase-9. Brain Res. 1436, 13-19. doi: 10.1016/j.brainres.2011.11.052
96. Zhang, X., Yu, J., Kuzontkoski, P. M., Zhu, W., Li, D. Y., and Groopman, J. E. (2012). Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability. PLoS Pathog. 8:e1002461. doi: 10.1371/journal.ppat.1002461
97. Zhong, Y., Zhang, B., Eum, S. Y., and Toborek, M. (2012). HIV-1 Tat triggers nuclear localization of ZO-1 via Rho signaling and cAMP response element-binding protein activation. J. Neurosci. 32, 143-150. doi: 10.1523/JNEUROSCI.4266-11.2012