Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Leah Christine Vines
 -- 1672 2023-10-31 15:18:07 |
2 update references and layout
Rita Xu
-26 word(s) 1646 2023-11-01 03:40:18 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Vines, L.; Sotelo, D.; Giddens, N.; Manza, P.; Volkow, N.D.; Wang, G. Co-Occurrence of Substance Use and HIV. Encyclopedia. Available online: https://encyclopedia.pub/entry/50999 (accessed on 31 July 2024).
Vines L, Sotelo D, Giddens N, Manza P, Volkow ND, Wang G. Co-Occurrence of Substance Use and HIV. Encyclopedia. Available at: https://encyclopedia.pub/entry/50999. Accessed July 31, 2024.
Vines, Leah, Diana Sotelo, Natasha Giddens, Peter Manza, Nora D. Volkow, Gene-Jack Wang. "Co-Occurrence of Substance Use and HIV" Encyclopedia, https://encyclopedia.pub/entry/50999 (accessed July 31, 2024).
Vines, L., Sotelo, D., Giddens, N., Manza, P., Volkow, N.D., & Wang, G. (2023, October 31). Co-Occurrence of Substance Use and HIV. In Encyclopedia. https://encyclopedia.pub/entry/50999
Vines, Leah, et al. "Co-Occurrence of Substance Use and HIV." Encyclopedia. Web. 31 October, 2023.
Co-Occurrence of Substance Use and HIV
Edit
This entry is adapted from the peer-reviewed paper 10.3390/brainsci13101480

Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH.

HIV-1 Tat gp120 psychostimulant use disorders

1. Introduction

The implementation of combined antiretroviral therapy (cART) in the global healthcare system has improved health-related quality of life for people living with HIV (PLWH). Historically, HIV was considered a terminal condition and has been recharacterized as a manageable chronic condition based on cART’s ability to reduce comorbidities and prolong survival [1][2]. Before the introduction of cART, PLWH exhibited severe HIV-associated neurocognitive disorders (HANDs) and accelerated brain aging, with more prominence during the late phases of HIV progression [3]. Currently, in the cART era, the prevalence of HAND remains high, albeit with reduced severity [3][4].
Over 80% of PLWH exhibit a lifetime history of trying an illicit drug, compared to 50% in the general population [5]. Additionally, PLWH exhibit a four times higher SUD prevalence than uninfected individuals [5]. Compared to other psychiatric disorders (i.e., depression, anxiety), SUDs are the most common comorbid conditions among PLWH (40–74% vs. <50%) [6]. Cocaine and methamphetamine (meth) use disorders (CUDs and MUDs, respectively) are associated with risky sexual behavior and needle sharing, increasing the likelihood of HIV transmission [7][8][9][10]. Additionally, a higher frequency of psychostimulant use has a greater negative impact on neurocognitive functioning in PLWH than in people living without HIV, pointing to the importance of addressing this dual diagnosis [11].
HIV and chronic psychostimulant misuse independently disrupt brain structure, function, and cognition [12][13][14][15][16][17]. The additive effects of HIV and chronic illicit psychostimulant use may be attributed in part to dysregulation of the dopamine system. Acute exposure to addictive substances transiently increases brain dopamine to supraphysiological levels, but chronic exposure attenuates dopamine signaling long-term, contributing to impairments in impulse control, learning, and memory [18]. Similarly, HIV significantly reduces dopamine synthesis, exacerbating HAND and disease progression [19][20][21].

2. Neuropathological Alterations in HIV and Evidence for Dopaminergic Dysfunction

The mechanism by which substance use contributes to HIV neuropathogenesis is not fully understood. HIV invades the central nervous system (CNS) within 1–2 weeks after the initial infection [22] through the transmigration of infected mature CD14+CD16+ monocytes across the blood-brain barrier (BBB) [23][24][25][26][27]. These cells can differentiate into long-lived macrophages and establish a viral reservoir within the CNS, infecting and activating myeloid cells, including microglia and macrophages, even with effective cART [28][29][30][31][32][33][34]. The infected and activated myeloid cells produce inflammatory cytokines and chemokines [35], leading to the recruitment and activation of additional myeloid populations and immune cells and damage to the BBB, resulting in chronic neuroinflammation [36]. Additionally, neurotoxic viral proteins such as Tat or gp120 that exacerbate the neurotoxic environment may also be released [37]. Studies also demonstrate that a small population of astrocytes harbor HIV DNA [38][39], but whether they are also viral reservoirs remains debated due to their low infectivity and replication rates [33][40][41][42]. A recent study demonstrated that although these reservoirs are low in number, HIV-infected astrocytes allow HIV to egress into the periphery, where they can repopulate the virus [43]. T-cells may also become infected and produce viruses in the CSF, which can circulate through the body and serve as a possible latent reservoir [44]. While neurons are poor viral reservoirs due to their lack of CD4 receptors, they are vulnerable to damage from chemokines, neurotoxins, and viral proteins such as Tat and gp120 [45]. Neurodegeneration is a hallmark feature of HAND, and both Tat and gp120 contribute to neurotoxicity through various mechanisms.
Tat, trans-activator of transcription, is the first viral protein to be transcribed and translated from the integrated HIV-1 provirus and is responsible for the recruitment of positive host transcription factor P-TEFb and recognition of the 5′TAR element in HIV-1 RNA, drastically increasing the rate of viral transcription [46][47][48]. Despite cART therapy, low levels of Tat expression can result in chronic glial activation, cytokine expression, and reductions in neuronal and synaptic density [49]. Exposure of primary microglial cells to Tat results in mitochondrial dysfunction and initiates mitophagy, activating microglia and neuroinflammation [50]. Injection of Tat into the caudate putamen of rats significantly increased levels of malondialdehyde (MDA), indicating oxidative damage and induction of neuronal apoptosis [51]. It has also been shown that Tat exposure can induce autophagy, resulting in a Tat-mediated downregulation of tight junction proteins and consequently increasing vascular permeability in an in vitro model of the BBB [52]. Tat also induces a presynaptic loss in rat hippocampal neurons associated with excessive Ca2+ influx via NMDAR [53].
Gp120, HIV envelope glycoprotein, progresses the pathogenesis of HAND by binding to co-receptors CCR5 and CXCR4 and allowing the virus to enter host cells [54]. Gp120 evokes synaptic and behavioral deficits in vivo that mirror significant features of HAND [55]. In vitro studies have also demonstrated gp120′s role in neurotoxicity. Exposure of primary rat cortical neurons to gp120 in vitro impairs mitochondrial function by decreasing the respiratory capacity of mitochondria and disrupting mitochondrial distribution [56]. Alterations in tight junction expression, morphological changes in brain microvascular endothelial cells, and increased stress fiber formation increase BBB permeability with gp120 exposure [57]. In human monocytes, gp120 induces the production of the cytokines TNF-a and IL-10, two proteins implicated in the immunopathology of HIV-1 [58]. An increase in NMDAR-mediated excitatory postsynaptic currents measured through whole-cell patch clamp recordings on hippocampal rat brain slices may involve a molecular mechanism for gp120-induced neuronal injury [59].
Despite the success of cART, the CNS continues to serve as a viral reservoir for toxins and cytokines. Tat and gp120 proteins are expressed in transgenic rodents to investigate the neurocognitive deficits observed in HAND [55][60][61]. In non-infectious HIV-1 transgenic rats, 7 of the 9 HIV proteins (env, Tat, rev, vif, vpr, vpu, and nef) are constitutively and systemically expressed and resemble HIV-1 seropositive individuals on cART [62]. Transgenic mice with gp120 expression constitutively express gp120 in astrocytes under the control of the promoter of glial fibrillary acidic protein (GFAP) [55]. Tat and gp120 expression in transgenic rodents have been used to study the combined effects of HIV-1 and psychostimulant drug exposure. Expressing these viral proteins in transgenic rodents can help elucidate mechanisms behind the altered dopaminergic systems observed in these comorbid conditions [63][64][65]. However, since these models only express some HIV-1 viral proteins, results from these models may miss the interactive and additive effects among these proteins.
Dopamine dysfunction has also been associated with HIV infection, and research has revealed selective damage to brain regions to which dopamine cells project, including the striatum [20][66]. While cART diminishes damage to these regions, PLWH on cART still shows striatal dysfunction, increased microglial activation, and inflammation, leading to neuronal damage [67][68][69][70][71]. Dopamine signaling has immunomodulatory effects by regulating the activation of myeloid and T-cells, the production of cytokines, transmigration, and phagocytosis [72][73][74][75], which could influence the development of HIV infection in the CNS and neurocognitive function. CD14+CD16+ monocytes, key mediators of HIV neuropathogenesis, express mRNA for all five dopamine receptors [73]. Dopamine and D1-like receptor agonists increased CD14+CD16+ cell motility, adhesion, and transmigration across the BBB in an in vitro model, suggesting that elevated extracellular dopamine in the CNS of PLWH with SUD contributes to HIV neuropathogenesis by increasing the accumulation of monocytes in dopamine-rich regions [72][73]. Elevated dopamine increases the susceptibility of macrophages to HIV [20] and spurs the production of inflammatory cytokines [76]. These effects of dopamine on immune function may promote the spread of viral infection, viral reservoirs, neuroinflammation, and neurotoxicity. Substance use is associated with increased HIV neuropathogenesis and neurocognitive decline in PLWH in the cART era [77][78][79][80], suggesting increased extracellular dopamine from substance use may play a role in the neurotoxic effects of HIV even when viral titers are very low.
Emerging evidence from pre-clinical studies suggests an HIV-mediated potentiation of drug reward [60][64][81][82][83]. These effects are theorized to be mediated by viral proteins, specifically Tat, which continues to be produced under viral suppression. Recent studies suggest that Tat may affect dopamine homeostasis by inhibiting dopamine transporter function allosterically, potentially elevating extracellular dopamine [84][85][86]. Psychostimulants, such as cocaine and meth, have complex interactions with Tat. Intravenous cocaine self-administration increased striatal DAT binding and showed an increased sensitivity to cocaine’s reinforcing effects in transgenic rats with Tat expression through a leftward shift in the dose-response curve [83]. Tat induces conformational changes in DAT that increase the affinity of cocaine for the transporter protein [87]. The similar and distinct effects of chronic cocaine administration and HIV-1 infection appear to enhance neurotoxicity, as evidenced by the overexcitation of mPFC pyramidal neurons in transgenic rats with Tat expression [88]. HIV-Tat and cocaine combined exposure in human and rat primary hippocampal neurons caused a significant depolarization of the mitochondrial membrane potential, indicative of mitochondrial damage. In contrast, Tat alone or cocaine alone only caused a slight effect on mitochondrial membrane potential [89].
Expression of Tat in transgenic mice augments methamphetamine-induced sensitization, as shown by increased locomotor activity and decreased expression of dopamine receptors demonstrated with RT-PCR and immunohistochemistry [64]. Like the mechanism of meth, Tat alters DA homeostasis by inhibiting DAT, and the combination of Tat and meth decreases DAT function more than either condition alone [90]. Increasing doses of meth resulted in impaired working and spatial memory in Tat transgenic mice compared to non-Tat or non-meth-treated mice, suggesting cooperative effects between Tat and meth on neurocognition [91]. Tat also increases microglial activation, indicating neuroinflammation [64]. Combined exposure to Tat and meth increased cellular ROS production, leading to neuronal injury [92]. In sum, these studies find that HIV infection enhances the effects of psychostimulants on dopaminergic pathways in the brain, including the reward pathway. This raises the possibility that PLWH have a greater risk of developing SUDs than those without HIV. Future studies examining compounds that can specifically block Tat binding site(s) in DAT and new forms of cART that do not affect normal DAT function, may provide an early intervention for mitigating the negative effects of HAND in PLWH with SUD.

References

  1. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: A collaborative analysis of 14 cohort studies. Lancet 2008, 372, 293–299.
  2. Tseng, A.; Seet, J.; Phillips, E.J. The evolution of three decades of antiretroviral therapy: Challenges, triumphs and the promise of the future: Three decades of antiretroviral therapy. Br. J. Clin. Pharmacol. 2015, 79, 182–194.
  3. Petersen, K.J.; Metcalf, N.; Cooley, S.; Tomov, D.; Vaida, F.; Paul, R.; Ances, B.M. Accelerated Brain Aging and Cerebral Blood Flow Reduction in Persons With Human Immunodeficiency Virus. Clin. Infect. Dis. 2021, 73, 1813–1821.
  4. Heaton, R.K.; Franklin, D.R.; Ellis, R.J.; McCutchan, J.A.; Letendre, S.L.; LeBlanc, S.; Corkran, S.H.; Duarte, N.A.; Clifford, D.B.; Woods, S.P.; et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors. J. Neurovirol. 2011, 17, 3–16.
  5. Shiau, S.; Arpadi, S.M.; Yin, M.T.; Martins, S.S. Patterns of drug use and HIV infection among adults in a nationally representative sample. Addict. Behav. 2017, 68, 39–44.
  6. Nedelcovych, M.T.; Manning, A.A.; Semenova, S.; Gamaldo, C.; Haughey, N.J.; Slusher, B.S. The Psychiatric Impact of HIV. ACS Chem. Neurosci. 2017, 8, 1432–1434.
  7. Koffarnus, M.N.; Johnson, M.W.; Thompson-Lake, D.G.Y.; Wesley, M.J.; Lohrenz, T.; Montague, P.R.; Bickel, W.K. Cocaine-dependent adults and recreational cocaine users are more likely than controls to choose immediate unsafe sex over delayed safer sex. Exp. Clin. Psychopharmacol. 2016, 24, 297–304.
  8. Kopetz, C.; Pickover, A.; Magidson, J.F.; Richards, J.M.; Iwamoto, D.; Lejuez, C.W. Gender and Social Rejection as Risk Factors for Engaging in Risky Sexual Behavior Among Crack/Cocaine Users. Prev. Sci. 2014, 15, 376–384.
  9. Roth, A.M.; Armenta, R.A.; Wagner, K.D.; Roesch, S.C.; Bluthenthal, R.N.; Cuevas-Mota, J.; Garfein, R.S. Patterns of Drug Use, Risky Behavior, and Health Status Among Persons Who Inject Drugs Living in San Diego, California: A Latent Class Analysis. Subst. Use Misuse 2015, 50, 205–214.
  10. Centers for Disease Control and Prevention. HIV Surveillance Report, 2017. 2018; Volume 29. Available online: http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html (accessed on 17 July 2023).
  11. Towe, S.L.; Tang, R.; Gibson, M.J.; Zhang, A.R.; Meade, C.S. Longitudinal changes in neurocognitive performance related to drug use intensity in a sample of persons with and without HIV who use illicit stimulantsLongitudinal effects of cocaine and HIV on cognitive performance. Drug Alcohol Depend. 2023, 251, 110923.
  12. Bak, Y.; Jun, S.; Choi, J.Y.; Lee, Y.; Lee, S.-K.; Han, S.; Shin, N.-Y. Altered intrinsic local activity and cognitive dysfunction in HIV patients: A resting-state fMRI study. PLoS ONE 2018, 13, e0207146.
  13. Bart, C.P.; Nusslock, R.; Ng, T.H.; Titone, M.K.; Carroll, A.L.; Damme, K.S.F.; Young, C.B.; Armstrong, C.C.; Chein, J.; Alloy, L.B. Decreased reward-related brain function prospectively predicts increased substance use. J. Abnorm. Psychol. 2021, 130, 886–898.
  14. Iudicello, J.E.; Woods, S.P.; Cattie, J.E.; Doyle, K.; Grant, I. Risky decision-making in HIV-associated neurocognitive disorders (HAND). Clin. Neuropsychol. 2013, 27, 256–275.
  15. Nestor, L.J.; Ersche, K.D. Abnormal Brain Networks Related to Drug and Nondrug Reward Anticipation and Outcome Processing in Stimulant Use Disorder: A Functional Connectomics Approach. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2023, 8, 560–571.
  16. Ottino-González, J.; Uhlmann, A.; Hahn, S.; Cao, Z.; Cupertino, R.B.; Schwab, N.; Allgaier, N.; Alia-Klein, N.; Ekhtiari, H.; Fouche, J.-P.; et al. White matter microstructure differences in individuals with dependence on cocaine, methamphetamine, and nicotine: Findings from the ENIGMA-Addiction working group. Drug Alcohol Depend. 2022, 230, 109185.
  17. Samboju, V.; Philippi, C.L.; Chan, P.; Cobigo, Y.; Fletcher, J.L.K.; Robb, M.; Hellmuth, J.; Benjapornpong, K.; Dumrongpisutikul, N.; Pothisri, M.; et al. Structural and functional brain imaging in acute HIV. NeuroImage Clin. 2018, 20, 327–335.
  18. Volkow, N.D.; Wise, R.A.; Baler, R. The dopamine motive system: Implications for drug and food addiction. Nat. Rev. Neurosci. 2017, 18, 741–752.
  19. Gaskill, P.J.; Calderon, T.M.; Luers, A.J.; Eugenin, E.A.; Javitch, J.A.; Berman, J.W. Human Immunodeficiency Virus (HIV) Infection of Human Macrophages Is Increased by Dopamine. Am. J. Pathol. 2009, 175, 1148–1159.
  20. Gaskill, P.J.; Yano, H.H.; Kalpana, G.V.; Javitch, J.A.; Berman, J.W. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages. PLoS ONE 2014, 9, e108232.
  21. Illenberger, J.M.; Harrod, S.B.; Mactutus, C.F.; McLaurin, K.A.; Kallianpur, A.; Booze, R.M. HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History. J. Neuroimmune Pharmacol. 2020, 15, 715–728.
  22. Dahl, V.; Peterson, J.; Fuchs, D.; Gisslen, M.; Palmer, S.; Price, R.W. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS 2014, 28, 2251–2258.
  23. Veenstra, M.; León-Rivera, R.; Li, M.; Gama, L.; Clements, J.E.; Berman, J.W. Mechanisms of CNS Viral Seeding by HIV+ CD14+ CD16+ Monocytes: Establishment and Reseeding of Viral Reservoirs Contributing to HIV-Associated Neurocognitive Disorders. mBio 2017, 8, e01280-17.
  24. Veenstra, M.; Williams, D.W.; Calderon, T.M.; Anastos, K.; Morgello, S.; Berman, J.W. Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: A potential therapeutic target for NeuroAIDS. J. Leukoc. Biol. 2017, 102, 1173–1185.
  25. Williams, D.; Veenstra, M.; Gaskill, P.; Morgello, S.; Calderon, T.; Berman, J. Monocytes Mediate HIV Neuropathogenesis: Mechanisms that Contribute to HIV Associated Neurocognitive Disorders. CHR 2014, 12, 85–96.
  26. Williams, D.W.; Calderon, T.M.; Lopez, L.; Carvallo-Torres, L.; Gaskill, P.J.; Eugenin, E.A.; Morgello, S.; Berman, J.W. 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.
  27. Williams, D.W.; Byrd, D.; Rubin, L.H.; Anastos, K.; Morgello, S.; Berman, J.W. CCR2 on CD14+CD16+ monocytes is a biomarker of HIV-associated neurocognitive disorders. Neurol. Neuroimmunol. Neuroinflamm. 2014, 1, e36.
  28. Abreu, C.M.; Veenhuis, R.T.; Avalos, C.R.; Graham, S.; Parrilla, D.R.; Ferreira, E.A.; Queen, S.E.; Shirk, E.N.; Bullock, B.T.; Li, M.; et al. Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques. mBio 2019, 10, e01659-19.
  29. Castellano, P.; Prevedel, L.; Eugenin, E.A. HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci. Rep. 2017, 7, 12866.
  30. Churchill, M.; Nath, A. Where does HIV hide? A focus on the central nervous system. Curr. Opin. HIV AIDS 2013, 8, 165–169.
  31. Honeycutt, J.B.; Wahl, A.; Baker, C.; Spagnuolo, R.A.; Foster, J.; Zakharova, O.; Wietgrefe, S.; Caro-Vegas, C.; Madden, V.; Sharpe, G.; et al. Macrophages sustain HIV replication in vivo independently of T cells. J. Clin. Investig. 2016, 126, 1353–1366.
  32. Honeycutt, J.B.; Thayer, W.O.; Baker, C.E.; Ribeiro, R.M.; Lada, S.M.; Cao, Y.; Cleary, R.A.; Hudgens, M.G.; Richman, D.D.; Garcia, J.V. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat. Med. 2017, 23, 638–643.
  33. Ko, A.; Kang, G.; Hattler, J.B.; Galadima, H.I.; Zhang, J.; Li, Q.; Kim, W.-K. Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy. J. Neuroimmune Pharmacol. 2019, 14, 110–119.
  34. Rappaport, J.; Volsky, D.J. Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment. J. Neurovirol. 2015, 21, 235–241.
  35. Arango Duque, G.; Descoteaux, A. Macrophage Cytokines: Involvement in Immunity and Infectious Diseases. Front. Immunol. 2014, 5, 491.
  36. Saylor, D.; Dickens, A.M.; Sacktor, N.; Haughey, N.; Slusher, B.; Pletnikov, M.; Mankowski, J.L.; Brown, A.; Volsky, D.J.; McArthur, J.C. HIV-associated neurocognitive disorder—pathogenesis and prospects for treatment. Nat. Rev. Neurol. 2016, 12, 234–248.
  37. Sanchez, A.; Kaul, M. Neuronal Stress and Injury Caused by HIV-1, cART and Drug Abuse: Converging Contributions to HAND. Brain Sci. 2017, 7, 25.
  38. Malik, S.; Valdebenito, S.; D’Amico, D.; Prideaux, B.; Eugenin, E.A. HIV infection of astrocytes compromises inter-organelle interactions and inositol phosphate metabolism: A potential mechanism of bystander damage and viral reservoir survival. Prog. Neurobiol. 2021, 206, 102157.
  39. Valdebenito, S.; Castellano, P.; Ajasin, D.; Eugenin, E.A. Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell-to-cell viral transfer. J. Neurochem. 2021, 158, 429–443.
  40. Barat, C.; Proust, A.; Deshiere, A.; Leboeuf, M.; Drouin, J.; Tremblay, M.J. Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency. Glia 2018, 66, 1363–1381.
  41. Chauhan, A. Enigma of HIV-1 latent infection in astrocytes: An in-vitro study using protein kinase C agonist as a latency reversing agent. Microbes Infect. 2015, 17, 651–659.
  42. Li, G.-H.; Henderson, L.; Nath, A. Astrocytes as an HIV Reservoir: Mechanism of HIV Infection. CHR 2016, 14, 373–381.
  43. Lutgen, V.; Narasipura, S.D.; Barbian, H.J.; Richards, M.; Wallace, J.; Razmpour, R.; Buzhdygan, T.; Ramirez, S.H.; Prevedel, L.; Eugenin, E.A.; et al. HIV infects astrocytes in vivo and egresses from the brain to the periphery. PLoS Pathog. 2020, 16, e1008381.
  44. Lustig, G.; Cele, S.; Karim, F.; Derache, A.; Ngoepe, A.; Khan, K.; Gosnell, B.I.; Moosa, M.-Y.S.; Ntshuba, N.; Marais, S.; et al. T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy. PLoS Pathog. 2021, 17, e1009871.
  45. Siddiqui, A.; He, C.; Lee, G.; Figueroa, A.; Slaughter, A.; Robinson-Papp, J. Neuropathogenesis of HIV and emerging therapeutic targets. Expert Opin. Ther. Targets 2022, 26, 603–615.
  46. Bagashev, A.; Sawaya, B.E. Roles and functions of HIV-1 Tat protein in the CNS: An overview. Virol. J. 2013, 10, 358.
  47. Jiang, Y.; Chai, L.; Fasae, M.B.; Bai, Y. The role of HIV Tat protein in HIV-related cardiovascular diseases. J. Transl. Med. 2018, 16, 121.
  48. Spector, C.; Mele, A.R.; Wigdahl, B.; Nonnemacher, M.R. Genetic variation and function of the HIV-1 Tat protein. Med. Microbiol. Immunol. 2019, 208, 131–169.
  49. Dickens, A.M.; Yoo, S.W.; Chin, A.C.; Xu, J.; Johnson, T.P.; Trout, A.L.; Hauser, K.F.; Haughey, N.J. Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging. Sci. Rep. 2017, 7, 7748.
  50. Thangaraj, A.; Periyasamy, P.; Liao, K.; Bendi, V.S.; Callen, S.; Pendyala, G.; Buch, S. HIV-1 TAT-mediated microglial activation: Role of mitochondrial dysfunction and defective mitophagy. Autophagy 2018, 14, 1596–1619.
  51. Louboutin, J.-P.; Agrawal, L.; Reyes, B.; Van Bockstaele, E.; Strayer, D. Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity. Antioxidants 2014, 3, 414–438.
  52. Liao, K.; Niu, F.; Hu, G.; Guo, M.-L.; Sil, S.; Buch, S. HIV Tat-mediated induction of autophagy regulates the disruption of ZO-1 in brain endothelial cells. Tissue Barriers 2020, 8, 1748983.
  53. Shin, A.H.; Thayer, S.A. Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures. Mol. Cell. Neurosci. 2013, 54, 22–29.
  54. Avdoshina, V.; Mocchetti, I. Recent Advances in the Molecular and Cellular Mechanisms of gp120-Mediated Neurotoxicity. Cells 2022, 11, 1599.
  55. Thaney, V.E.; Sanchez, A.B.; Fields, J.A.; Minassian, A.; Young, J.W.; Maung, R.; Kaul, M. Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research. J. Neurovirol. 2018, 24, 156–167.
  56. Avdoshina, V.; Fields, J.A.; Castellano, P.; Dedoni, S.; Palchik, G.; Trejo, M.; Adame, A.; Rockenstein, E.; Eugenin, E.; Masliah, E.; et al. The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons. Neurotox Res. 2016, 29, 583–593.
  57. McRae, M. HIV and viral protein effects on the blood brain barrier. Tissue Barriers 2016, 4, e1143543.
  58. Planès, R.; Serrero, M.; Leghmari, K.; BenMohamed, L.; Bahraoui, E. HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway. Sci. Rep. 2018, 8, 17215.
  59. Zhou, Y.; Liu, J.; Xiong, H. HIV-1 Glycoprotein 120 Enhancement of N-Methyl-D-Aspartate NMDA Receptor-Mediated Excitatory Postsynaptic Currents: Implications for HIV-1-Associated Neural Injury. J. Neuroimmune Pharmacol. 2017, 12, 314–326.
  60. Moran, L.M.; Booze, R.M.; Webb, K.M.; Mactutus, C.F. Neurobehavioral alterations in HIV-1 transgenic rats: Evidence for dopaminergic dysfunction. Exp. Neurol. 2013, 239, 139–147.
  61. Repunte-Canonigo, V.; Lefebvre, C.; George, O.; Kawamura, T.; Morales, M.; Koob, G.F.; Califano, A.; Masliah, E.; Sanna, P.P. Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats. Mol. Neurodegener. 2014, 9, 26.
  62. McLaurin, K.A.; Li, H.; Booze, R.M.; Mactutus, C.F. Disruption of Timing: NeuroHIV Progression in the Post-cART Era. Sci. Rep. 2019, 9, 827.
  63. Gaskill, P.J.; Miller, D.R.; Gamble-George, J.; Yano, H.; Khoshbouei, H. HIV, Tat and dopamine transmission. Neurobiol. Dis. 2017, 105, 51–73.
  64. Kesby, J.P.; Najera, J.A.; Romoli, B.; Fang, Y.; Basova, L.; Birmingham, A.; Marcondes, M.C.G.; Dulcis, D.; Semenova, S. HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function. Brain Behav. Immun. 2017, 65, 210–221.
  65. Namba, M.D.; Phillips, M.N.; Chen, P.-J.; Blass, B.E.; Olive, M.F.; Neisewander, J.L. HIV gp120 impairs nucleus accumbens neuroimmune function and dopamine D3 receptor-mediated inhibition of cocaine seeking in male rats. Addict. Neurosci. 2023, 5, 100062.
  66. Fitting, S.; Booze, R.M.; Mactutus, C.F. HIV-1 proteins, Tat and gp120, target the developing dopamine system. Curr. HIV Res. 2015, 13, 21–42.
  67. Du Plessis, S.; Vink, M.; Joska, J.A.; Koutsilieri, E.; Bagadia, A.; Stein, D.J.; Emsley, R. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI. J. Int. Neuropsychol. Soc. 2015, 21, 722–731.
  68. Gongvatana, A.; Harezlak, J.; Buchthal, S.; Daar, E.; Schifitto, G.; Campbell, T.; Taylor, M.; Singer, E.; Algers, J.; Zhong, J.; et al. Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J. Neurovirol. 2013, 19, 209–218.
  69. Ipser, J.C.; Brown, G.G.; Bischoff-Grethe, A.; Connolly, C.G.; Ellis, R.J.; Heaton, R.K.; Grant, I. Translational Methamphetamine AIDS Research Center (TMARC) Group HIV Infection Is Associated with Attenuated Frontostriatal Intrinsic Connectivity: A Preliminary Study. J. Int. Neuropsychol. Soc. 2015, 21, 203–213.
  70. Tavazzi, E.; Morrison, D.; Sullivan, P.; Morgello, S.; Fischer, T. Brain Inflammation is a Common Feature of HIV-Infected Patients without HIV Encephalitis or Productive Brain Infection. CHR 2014, 12, 97–110.
  71. Vera, J.H.; Guo, Q.; Cole, J.H.; Boasso, A.; Greathead, L.; Kelleher, P.; Rabiner, E.A.; Kalk, N.; Bishop, C.; Gunn, R.N.; et al. Neuroinflammation in treated HIV-positive individuals: A TSPO PET study. Neurology 2016, 86, 1425–1432.
  72. Calderon, T.M.; Williams, D.W.; Lopez, L.; Eugenin, E.A.; Cheney, L.; Gaskill, P.J.; Veenstra, M.; Anastos, K.; Morgello, S.; Berman, J.W. Dopamine Increases CD14+CD16+ Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis. J. Neuroimmune Pharmacol. 2017, 12, 353–370.
  73. Coley, J.S.; Calderon, T.M.; Gaskill, P.J.; Eugenin, E.A.; Berman, J.W. Dopamine Increases CD14+CD16+ Monocyte Migration and Adhesion in the Context of Substance Abuse and HIV Neuropathogenesis. PLoS ONE 2015, 10, e0117450.
  74. Nolan, R.; Gaskill, P.J. The role of catecholamines in HIV neuropathogenesis. Brain Res. 2019, 1702, 54–73.
  75. Yan, Y.; Jiang, W.; Liu, L.; Wang, X.; Ding, C.; Tian, Z.; Zhou, R. Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome. Cell 2015, 160, 62–73.
  76. Nolan, R.A.; Muir, R.; Runner, K.; Haddad, E.K.; Gaskill, P.J. Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders. J. Neuroimmune Pharmacol. 2019, 14, 134–156.
  77. Blackstone, K.; Iudicello, J.E.; Morgan, E.E.; Weber, E.; Moore, D.J.; Franklin, D.R.; Ellis, R.J.; Grant, I.; Woods, S.P. Human Immunodeficiency Virus Infection Heightens Concurrent Risk of Functional Dependence in Persons With Long-Term Methamphetamine Use. J. Addict. Med. 2013, 7, 255–263.
  78. Jacobs, M.M.; Murray, J.; Byrd, D.A.; Hurd, Y.L.; Morgello, S. HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations. J. Neurovirol. 2013, 19, 495–504.
  79. Meade, C.S.; Addicott, M.; Hobkirk, A.L.; Towe, S.L.; Chen, N.-K.; Sridharan, S.; Huettel, S.A. Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice: Cocaine and HIV BOLD activity. Addict. Biol. 2018, 23, 796–809.
  80. Meyer, V.J.; Little, D.M.; Fitzgerald, D.A.; Sundermann, E.E.; Rubin, L.H.; Martin, E.M.; Weber, K.M.; Cohen, M.H.; Maki, P.M. Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection. J. Neurovirol. 2014, 20, 352–361.
  81. Paris, J.J.; Carey, A.N.; Shay, C.F.; Gomes, S.M.; He, J.J.; McLaughlin, J.P. Effects of Conditional Central Expression of HIV-1 Tat Protein to Potentiate Cocaine-Mediated Psychostimulation and Reward Among Male Mice. Neuropsychopharmacology 2014, 39, 380–388.
  82. Huynh, Y.W.; Thompson, B.M.; Larsen, C.E.; Buch, S.; Guo, M.; Bevins, R.A.; Murray, J.E. Male HIV-1 transgenic rats show reduced cocaine-maintained lever-pressing compared to F344 wildtype rats despite similar baseline locomotion. J. Exper. Anal. Behav. 2020, 113, 468–484.
  83. McIntosh, S.; Sexton, T.; Pattison, L.P.; Childers, S.R.; Hemby, S.E. Increased Sensitivity to Cocaine Self-Administration in HIV-1 Transgenic Rats is Associated with Changes in Striatal Dopamine Transporter Binding. J. Neuroimmune Pharmacol. 2015, 10, 493–505.
  84. Midde, N.M.; Yuan, Y.; Quizon, P.M.; Sun, W.-L.; Huang, X.; Zhan, C.-G.; Zhu, J. Mutations at Tyrosine 88, Lysine 92 and Tyrosine 470 of Human Dopamine Transporter Result in an Attenuation of HIV-1 Tat-Induced Inhibition of Dopamine Transport. J. Neuroimmune Pharmacol. 2015, 10, 122–135.
  85. Yuan, Y.; Huang, X.; Midde, N.M.; Quizon, P.M.; Sun, W.-L.; Zhu, J.; Zhan, C.-G. Molecular Mechanism of HIV-1 Tat Interacting with Human Dopamine Transporter. ACS Chem. Neurosci. 2015, 6, 658–665.
  86. Yuan, Y.; Quizon, P.M.; Sun, W.-L.; Yao, J.; Zhu, J.; Zhan, C.-G. Role of Histidine 547 of Human Dopamine Transporter in Molecular Interaction with HIV-1 Tat and Dopamine Uptake. Sci. Rep. 2016, 6, 27314.
  87. Midde, N.M.; Huang, X.; Gomez, A.M.; Booze, R.M.; Zhan, C.-G.; Zhu, J. Mutation of Tyrosine 470 of Human Dopamine Transporter is Critical for HIV-1 Tat-Induced Inhibition of Dopamine Transport and Transporter Conformational Transitions. J. Neuroimmune Pharmacol. 2013, 8, 975–987.
  88. Wayman, W.N.; Chen, L.; Persons, A.L.; Napier, T.C. Cortical consequences of HIV-1 Tat exposure in rats are enhanced by chronic cocaine. Curr. HIV Res. 2015, 13, 80–87.
  89. De Simone, F.I.; Darbinian, N.; Amini, S.; Muniswamy, M.; White, M.K.; Elrod, J.W.; Datta, P.K.; Langford, D.; Khalili, K. HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a Mitochondrial Pathway. J. Neuroimmune Pharmacol. 2016, 11, 358–368.
  90. Appadoo, C.N.; Sambo, D.; Alonge, T.; Harvey, B.; Khoshbouei, H. The Dual Effect of HIV-1 Tat and Methamphetamine on Dopamine Transporter Function. FASEB J. 2017, 31, 662.10.
  91. Nookala, A.R.; Schwartz, D.C.; Chaudhari, N.S.; Glazyrin, A.; Stephens, E.B.; Berman, N.E.J.; Kumar, A. Methamphetamine augment HIV-1 Tat mediated memory deficits by altering the expression of synaptic proteins and neurotrophic factors. Brain Behav. Immun. 2018, 71, 37–51.
  92. Zeng, X.-F.; Li, Q.; Li, J.; Wong, N.; Li, Z.; Huang, J.; Yang, G.; Sham, P.C.; Li, S.-B.; Lu, G. HIV-1 Tat and methamphetamine co-induced oxidative cellular injury is mitigated by N-acetylcysteine amide (NACA) through rectifying mTOR signaling. Toxicol. Lett. 2018, 299, 159–171.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Neurosciences
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Leah Vines
,
Diana Sotelo
,
Natasha Giddens
,
Peter Manza
,
Nora D. Volkow
,
Gene-Jack Wang
View Times: 278
Revisions: 2 times (View History)
Update Date: 01 Nov 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback