Mechanisms of Blood-Retinal Barrier Disruption by HIV-1

Author(s): Yiwen Qian, Xin Che, Jing Jiang, Zhiliang Wang*.

Journal Name: Current HIV Research

Volume 17 , Issue 1 , 2019

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Graphical Abstract:


It has been found that human immunodeficiency virus (HIV)-1 RNA or antigens can be detected in the intraocular tissues of HIV-1 patients even under effective highly active anti-retroviral therapy (HAART). In vivo, blood-retinal barrier (BRB) establishes a critical, physiological guardian against microbial invasion of the eye, but may be compromised in the presence of HIV-1. The envelope glycoprotein gp120 is exposed on the surface of the HIV envelope, essential for virus entry into cells by the attachment to specific cell surface receptors. The BRB disruption by glycoprotein gp120 has been widely recognized, which is toxic to human retinal epithelial cells (RPE) and umbilical vein endothelial cells (HUVEC). The present review elaborates on various mechanisms of BRB disruption induced by HIV gp120, which may represent potential targets for the prevention of ocular HIV complications in the future.

Keywords: Blood-retinal barrier, HIV gp120, tight junction proteins, inflammatory cytokines, oxidative stress, MMPs.

Cunningham ET Jr, Margolis TP. Ocular manifestations of HIV infection. N Engl J Med 1998; 339: 236-44.
Kestelyn PG, Cunningham ET Jr. HIV/AIDS and blindness. Bull World Health Organ 2001; 79: 208-13.
Vrabec TR. Posterior segment manifestations of HIV/AIDS. Survey of ophthalmology 2004; 49: 131-57.
Martin-Odoom A, Bonney EY, Opoku DK. Ocular complications in HIV positive patients on antiretroviral therapy in Ghana. BMC Ophthalmol 2016; 16: 134.
Wang Z, Jia R, Ge S, et al. Ocular complications of human immunodeficiency virus infection in eastern china. Am J Ophthalmol 2012; 153: 363-9.
Han Y, Wu N, Zhu W, et al. Detection of HIV-1 viruses in tears of patients even under long-term HAART. AIDS 2011; 25: 1925-7.
Peng CH, Chen SJ, Ho CK, et al. Detection of HIV RNA levels in intraocular and cerebrospinal fluids in patients with AIDS-related cryptococcosis. Ophthalmologica 2005; 219: 101-6.
Hsu WM, Chiou SH, Chen SS, et al. The HIV RNA levels of plasma and ocular fluids in aids patients with ophthalmic infections. Ophthalmologica 2004; 218: 328-32.
Niederkorn JY. Immune privilege and immune regulation in the eye. Adv Immunol 1990; 48: 191-226.
Persidsky Y, Poluektova L. Immune privilege and HIV-1 persistence in the CNS. Immunol Rev 2006; 213: 180-94.
Head JR, Billingham RE. Immune privilege in the testis. II. Evaluation of potential local factors. Transplantation 1985; 40: 269-75.
Taylor AW, Ng TF. Negative regulators that mediate ocular immune privilege. J Leukoc Biol 2018. [Epub ahead of print].
Taylor AW. Ocular immune privilege. Eye (Lond) 2009; 23: 1885-9.
Kaplan HJ, Streilein JW. Immune response to immunization via the anterior chamber of the eye. II. An analysis of F1 lymphocyte-induced immune deviation. 1978. Ocul Immunol Inflamm 2007; 15: 179-85.
Streilein JW. Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003; 74: 179-85.
de Andrade FA, Fiorot SH, Benchimol EI, Provenzano J, Martins VJ, Levy RA. The autoimmune diseases of the eyes. Autoimmun Rev 2016; 15: 258-71.
Taylor AW, Alard P, Yee DG, Streilein JW. Aqueous humor induces transforming growth factor-beta (TGF-beta)-producing regulatory T-cells. 1997. Ocul Immunol Inflamm 2007; 15: 215-24.
Taylor AW, Streilein JW, Cousins SW. Immunoreactive vasoactive intestinal peptide contributes to the immunosuppressive activity of normal aqueous humor. J Immunol 1994; 153: 1080-6.
Cunha-Vaz JG. The blood-ocular barriers: past, present, and future. Doc Ophthalmol 1997; 93: 149-57.
Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57: 173-85.
Wang Z, Jia R, Ge S, et al. Ocular complications of human immunodeficiency virus infection in eastern china. Am J Ophthalmol 2012; 153: 363-9.
Ng WT, Versace P. Ocular association of HIV infection in the era of highly active antiretroviral therapy and the global perspective. Clin Experiment Ophthalmol 2005; 33: 317-29.
Kempen JH, Jabs DA, Wilson LA, Dunn JP, West SK, Tonascia J. Mortality risk for patients with cytomegalovirus retinitis and acquired immune deficiency syndrome. Clin Infect Dis 2003; 37: 1365-73.
Jabs DA. Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc 1995; 93: 623-83.
Erickson KK, Sundstrom JM, Antonetti DA. Vascular permeability in ocular disease and the role of tight junctions. Angiogenesis 2007; 10: 103-17.
Hellstrom M, Gerhardt H, Kalen M, et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 2001; 153: 543-53.
Rizzolo LJ. Polarity and the development of the outer blood-retinal barrier. Histol Histopathol 1997; 12: 1057-67.
Runkle EA, Antonetti DA. The blood-retinal barrier: structure and functional significance. Methods Mol Biol 2011; 686: 133-48.
Cunha-Vaz J, Bernardes R, Lobo C. Blood-retinal barrier. Eur J Ophthalmol 2011; 21(Suppl. 6): S3-9.
Gonzalez-Mariscal L, Betanzos A, Nava P, Jaramillo BE. Tight junction proteins. Prog Biophys Mol Biol 2003; 81: 1-44.
Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation. Adv Drug Deliv Rev 2005; 57: 883-917.
Gonzalez-Mariscal L. A. B, Nava P, Jaramillo BE. Tight junction proteins. Prog Biophys Mol Biol 2003; 81: 1-44.
Ramirez SH, Hasko J, Skuba A, et al. Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. J Neurosci 2012; 32: 4004-16.
Williams LA, Martin-Padura I, Dejana E, Hogg N, Simmons DL. Identification and characterisation of human junctional adhesion molecule (JAM). Mol Immunol 1999; 36: 1175-88.
Tietz S, Engelhardt B. Brain barriers: Crosstalk between complex tight junctions and adherens junctions. J Cell Biol 2015; 209: 493-506.
Miyoshi J, Takai Y. Molecular perspective on tight-junction assembly and epithelial polarity. Adv Drug Deliv Rev 2005; 57: 815-55.
Kuznik BI, Linkova NS, Kolchina NV, Kukanova EO, Khavinson VK. The JAM family of molecules and their role in the regulation of physiological and pathological processes. Usp Fiziol Nauk 2016; 47(4): 76-97.
Economopoulou M, Avramovic N, Klotzsche-von Ameln A, et al. Endothelial-specific deficiency of junctional adhesion molecule-C promotes vessel normalisation in proliferative retinopathy. Thromb Haemost 2015; 114: 1241-9.
Wittchen ES, Haskins J, Stevenson BR. Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3. J Biol Chem 1999; 274(49): 35179-85.
Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol 1998; 141: 199-208.
Gumbiner B, Lowenkopf T, Apatira D. Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc Natl Acad Sci USA 1991; 88: 3460-4.
Lu L, Yu F, Cai L, Debnath AK, Jiang S. Development of small-molecule HIV entry inhibitors specifically targeting gp120 or gp41. Curr Top Med Chem 2016; 16: 1074-90.
Geijtenbeek TB, Kwon DS, Torensma R, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100: 587-97.
Arthos J, Cicala C, Martinelli E, et al. HIV-1 envelope protein binds to and signals through integrin alpha(4)beta(7), the gut mucosal homing receptor for peripheral T cells. Nat Immunol 2008; 9: 301-9.
Vivès RR, Anne I, Sattentau QJ, Hugues LJ. Heparan sulfate targets the HIV-1 envelope glycoprotein gp120 coreceptor binding site. J Biol Chem 2005; 280: 21353-7.
Ahmed Z, Kawamura T, Shimada S, Piguet V. The role of human dendritic cells in HIV-1 infection. J Invest Dermatol 2015; 135: 1225-33.
Wu L. KewalRamani VN. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 2006; 6: 859-68.
Geijtenbeek TB, van Kooyk Y. DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission. Curr Top Microbiol Immunol 2003; 276: 31-54.
Geijtenbeek TB, Kwon DS, Torensma R, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100: 587-97.
Dohgu S, Ryerse JS, Robinson SM, Banks WA. Human immunodeficiency virus-1 uses the mannose-6-phosphate receptor to cross the blood-brain barrier. PLoS One 2012; 7: e39565.
Canki M, Sparrow JR, Chao W, Potash MJ, Volsky DJ. Human immunodeficiency virus type 1 can infect human retinal pigment epithelial cells in culture and alter the ability of the cells to phagocytose rod outer segment membranes. AIDS Res Hum Retroviruses 2000; 16(5): 453-63.
Wan ZT, Chen XL. Mechanisms of HIV envelope-induced T lymphocyte apoptosis. Virol Sin 2010; 25: 307-15.
Cummins NW, Rizza SA, Badley AD. How much gp120 is there? J Infect Dis 2010; 201: 1273-4.
Ellaurie M, Calvelli TA, Rubinstein A. Human immunodeficiency virus (HIV) circulating immune complexes in infected children. AIDS Res Hum Retroviruses 1990; 6: 1437-41.
Hasebe R, Suzuki T, Makino Y, et al. Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein. BMC Microbiol 2010; 10: 165.
Verma S, Lo Y, Chapagain M, et al. West Nile virus infection modulates human brain microvascular endothelial cells tight junction proteins and cell adhesion molecules: Transmigration across the in vitro blood-brain barrier. Virology 2009; 385: 425-33.
Nazli A, Kafka JK, Ferreira VH, et al. HIV-1 gp120 induces TLR2- and TLR4-mediated innate immune activation in human female genital epithelium. J Immunol 2013; 191: 4246-58.
Louboutin J-P, Reyes BAS, Agrawal L, Van Bockstaele EJ, Strayer DS. HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy. Eur J Neurosci 2011; 34: 2015-23.
Louboutin JP, Strayer DS. Blood-brain barrier abnormalities caused by HIV-1 gp120: Mechanistic and therapeutic implications. Sci World J 2012; 2012: 482575.
Craigo JK, Gupta P. HIV-1 in genital compartments: vexing viral reservoirs. Curr Opin HIV AIDS 2006; 1: 97-102.
Cioni C, Annunziata P. Circulating gp120 alters the blood-brain barrier permeability in HIV-1 gp120 transgenic mice. Neurosci Lett 2002; 330: 299-301.
Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol 2002; 47(Suppl. 2): S253-62.
Shah A, Singh DP, Buch S, Kumar A. HIV-1 envelope protein gp120 up regulates CCL5 production in astrocytes which can be circumvented by inhibitors of NF-kappaB pathway. Biochemical and biophysical research communications 2011; 414: 112-7.
Yin PD, Kurup SK, Fischer SH, et al. Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR. J Clin Virol 2007; 38: 254-9.
Sanyal S, Zeilmaker GH. Cell lineage in retinal development of mice studied in experimental chimaeras. Nature 1977; 265(5596): 731-3.
Power C, Gill MJ, Johnson RT. Progress in clinical neurosciences: The neuropathogenesis of HIV infection: host-virus interaction and the impact of therapy. Can J Neurol Sci 2002; 29: 19-32.
Woollard SM, Bhargavan B, Yu F, Kanmogne GD. Differential effects of Tat proteins derived from HIV-1 subtypes B and recombinant CRF02_AG on human brain microvascular endothelial cells: implications for blood-brain barrier dysfunction. J Cereb Blood Flow Metab 2014; 34: 1047-59.
Qian YW, Li C, Jiang AP, et al. HIV-1 gp120 glycoprotein interacting with dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) down-regulates tight junction proteins to disrupt the blood retinal barrier and increase its permeability. J Biol Chem 2016; 291(44): 22977-87.
Lee IT, Liu SW, Chi PL, Lin CC, Hsiao LD, Yang CM. TNF-alpha mediates PKCdelta/JNK1/2/c-Jun-dependent monocyte adhesion via ICAM-1 induction in human retinal pigment epithelial cells. PLoS One 2015; 10(2): e0117911.
Kolb SA, Sporer B, Lahrtz F, Koedel U, Pfister HW, Fontana A. Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-gamma inducible protein 10. J Neuroimmunol 1999; 93(1-2): 172-81.
Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW. 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 2006; 26(4): 1098-106.
Shah A, Verma AS, Patel KH, Noel R, Rivera-Amill V, Silverstein PS, et al. HIV-1 gp120 induces expression of IL-6 through a nuclear factor-kappa B-dependent mechanism: suppression by gp120 specific small interfering RNA. PLoS One 2011; 6: e21261.
Sarkar R, Mitra D, Chakrabarti S. HIV-1 gp120 protein downregulates Nef induced IL-6 release in immature dentritic cells through interplay of DC-SIGN. PLoS One 2013; 8: e59073.
Borgmann K, Ghorpade A. HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads. Front Microbiol 2015; 6: 1143.
Yu QR, Zhang ZP, Zhang H, et al. Inducible nitric oxide synthase is involved in the oxidation stress induced by HIV-1 gp120 in human retina pigment epithelial cells. Chin Med J (Engl) 2008; 121(24): 2578-83.
Silverstein PS, Shah A, Weemhoff J, Kumar S, Singh DP, Kumar A. HIV-1 gp120 and drugs of abuse: interactions in the central nervous system. Curr HIV Res 2012; 10(5): 369-83.
Louboutin JP, Agrawal L, Reyes BA, Van Bockstaele EJ, Strayer DS. 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 2010; 69: 801-16.
Banerjee A, Zhang X, Manda KR, Banks WA, Ercal N. HIV proteins (gp120 and Tat) and methamphetamine in oxidative stressinduced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide. Free Radic Biol Med 2010 15; 48(10): 1388-98.
Silverstein PS, Shah A, Weemhoff J, Kumar S, Singh DP, Kumar A. HIV-1 gp120 and drugs of abuse: interactions in the central nervous system. Curr HIV Res 2012; 10: 369-83.
Price TO, Uras F, Banks WA, Ercal N. A novel antioxidant N-acetylcysteine amide prevents gp120- and Tat-induced oxidative stress in brain endothelial cells. Exp Neurol 2006; 201: 193-202.
Price TO, Ercal N, Nakaoke R, Banks WA. HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells. Brain Res 2005; 1045: 57-63.
Chatterjee N, Callen S, Seigel GM, Buch SJ. HIV-1 Tat-mediated neurotoxicity in retinal cells. J Neuroimmune Pharmacol 2011; 6: 399-408.
Louboutin JP, Reyes BA, Agrawal L, Maxwell CR, Van Bockstaele EJ, Strayer DS. Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes. Neurobiol Dis 2010; 38(2): 313-25.
Hoffmann S, He S, Ehren M, Ryan SJ, Wiedemann P, Hinton DR. MMP-2 and MMP-9 secretion by rpe is stimulated by angiogenic molecules found in choroidal neovascular membranes. Retina 2006; 26: 454-61.
Lambert V, Wielockx B, Munaut C, et al. MMP-2 and MMP-9 synergize in promoting choroidal neovascularization. FASEB J 2003; 17: 2290-2.
Singh D, Srivastava SK, Chaudhuri TK, Upadhyay G. Multifaceted role of matrix metalloproteinases (MMPs). Front Mol Biosci 2015; 2: 19.
Sporer B, Paul R, Koedel U, et al. Presence of matrix metalloproteinase-9 activity in the cerebrospinal fluid of human immunodeficiency virus-infected patients. J Infect Dis 1998; 178(3): 854-7.
Persidsky Y, Limoges J, Rasmussen J, Zheng J, Gearing A, Gendelman HE. Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis. J Neuroimmunol 2001; 114: 57-68.
Rajashekhar G, Shivanna M, Kompella UB, Wang Y, Srinivas SP. Role of MMP-9 in the breakdown of barrier integrity of the corneal endothelium in response to TNF-alpha. Exp Eye Res 2014; 122: 77-85.
Xing Y, Shepherd N, Lan J, et al. MMPs/TIMPs imbalances in the peripheral blood and cerebrospinal fluid are associated with the pathogenesis of HIV-1-associated neurocognitive disorders. Brain Behav Immun 2017; 65: 161-72.
Tsai HC, Ye SY, Kunin CM, et al. Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis. Cytokine 2011; 54(2): 109-16.
Gurney KJ, Estrada EY, Rosenberg GA. Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol Dis 2006; 23: 87-96.
Reijerkerk A, Kooij G, van der Pol SM, Khazen S, Dijkstra CD, de Vries HE. Diapedesis of monocytes is associated with MMP-mediated occludin disappearance in brain endothelial cells. FASEB J 2006; 20: 2550-2.
Giebel SJ, Menicucci G, McGuire PG, Das A. Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Lab Invest 2005; 85: 597-607.
Steen B, Sejersen S, Berglin L, Seregard S, Kvanta A. Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci 1998; 39: 2194-200.
Runkle EA, Mu D. Tight junction proteins: from barrier to tumorigenesis. Cancer Lett 2013; 337: 41-8.
Kanmogne GD, Schall K, Leibhart J, Knipe B, Gendelman HE, Persidsky Y. 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 2007; 27: 123-34.
Strazza M, Pirrone V, Wigdahl B, Nonnemacher MR. Breaking down the barrier: the effects of HIV-1 on the blood-brain barrier. Brain Res 2011; 1399: 96-115.
Tan S, Duan H, Xun T, et al. HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy. Laboratory investigation; a journal of technical methods and pathology 2014; 94: 777-87.
Gandhi N, Saiyed ZM, Napuri J. Interactive role of human immunodeficiency virus type 1 (HIV-1) clade-specific Tat protein and cocaine in blood-brain barrier dysfunction: implications for HIV-1-associated neurocognitive disorder. J Neurovirol 2010; 16(4): 294-305.
Kanmogne GD, Primeaux C, Grammas P. 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 2005; 64(6): 498-505.
Buckner CM, Calderon TM, Willams DW, Belbin TJ, Berman JW. Characterization of monocyte maturation/differentiation that facilitates their transmigration across the blood-brain barrier and infection by HIV: implications for NeuroAIDS. Cell Immunol 2011; 267: 109-23.
Wu DT, Woodman SE, Weiss JM, et al. Mechanisms of leukocyte trafficking into the CNS. J Neurovirol 2000; 6(Suppl. 1): S82-5.
Williams DW, Calderon TM, Lopez L, et al. Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One 2013; 8: e69270.
Bai L, Zhu X, Ma T, et al. The p38 MAPK NF-kappaB pathway, not the ERK pathway, is involved in exogenous HIV-1 Tat-induced apoptotic cell death in retinal pigment epithelial cells. Int J Biochem Cell Biol 2013; 45(8): 1794-801.
Bai L, Zhang Z, Zhang H, et al. HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: an in vitro study. BMC Infect Dis 2008; 8: 77.
Heiden D, Tun N, Smithuis FN, et al. Active cytomegalovirus retinitis after the start of antiretroviral therapy. Br J Ophthalmol 2019; 103: 157-60.
Haile WB, Gavegnano C, Tao S, Jiang Y, Schinazi RF, Tyor WR. The Janus kinase inhibitor ruxolitinib reduces HIV replication in human macrophages and ameliorates HIV encephalitis in a murine model Neurobiol Dis 2016; 92(Pt B): 137-43
Mahajan SD, Aalinkeel R, Law WC, et al. Anti-HIV-1 nanotherapeutics: promises and challenges for the future. Int J Nanomedicine 2012; 7: 5301-14.
Saiyed ZM, Gandhi NH, Nair MP. Magnetic nanoformulation of azidothymidine 5′-triphosphate for targeted delivery across the blood-brain barrier. Int J Nanomedicine 2010; 5: 157-66.
Ding H, Sagar V, Agudelo M, et al. Enhanced blood-brain barrier transmigration using a novel transferrin embedded fluorescent magneto-liposome nanoformulation. Nanotechnology 2014; 25(5): 055101.
Atluri V, Pilakka-Kanthikeel S, Samikkannu T, et al. 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 2014; 7: 37.
Jayant RD, Atluri VS, Agudelo M, Sagar V, Kaushik A, Nair M. Sustained-release nanoART formulation for the treatment of neuroAIDS. Int J Nanomedicine 2015; 10: 1077-93.
Dutta L, Mukherjee B, Chakraborty T, et al. Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood-brain barrier into brain. Drug Deliv 2018; 25(1): 504-16.
Roy U, Drozd V, Durygin A, et al. Characterization of Nanodiamond-based anti-HIV drug Delivery to the Brain. Sci Rep 2018; 8(1): 1603.
Schaftenaar E, Khosa NS, Baarsma GS, et al. HIV-infected individuals on long-term antiretroviral therapy are at higher risk for ocular disease. Epidemiol Infect 2017; 145(12): 2520-9.
Huang W, Eum SY, Andras IE, Hennig B, Toborek M. PPARalpha and PPARgamma attenuate HIV-induced dysregulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities. FASEB J 2009; 23: 1596-606.
Huang W, Chen L, Zhang B, Park M, Toborek M. PPAR agonist-mediated protection against HIV Tat-induced cerebrovascular toxicity is enhanced in MMP-9-deficient mice. J Cereb Blood Flow Metab 2014; 34(4): 646-53.
Ramirez SH, Heilman D, Morsey B, Potula R, Haorah J, Persidsky Y. Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) suppresses Rho GTPases in human brain microvascular endothelial cells and inhibits adhesion and transendothelial migration of HIV-1 infected monocytes. J Immunol 2008; 180(3): 1854-65.
Singh VB, Singh MV, Gorantla S, Poluektova LY, Maggirwar SB. Smoothened agonist reduces human immunodeficiency virus type-1-induced blood-brain barrier breakdown in humanized mice. Sci Rep 2016; 6: 26876.

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Year: 2019
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