Top

Published in:

01-12-2020 | Alzheimer's Disease | Review

Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders

Authors: Xue Chen, Tong Zhang, Yulin Zhang

Published in: Journal of NeuroVirology | Issue 6/2020

Abstract

Although antiretroviral therapy (ART) affects virologic suppression and prolongs life expectancies among HIV-positive patients; HIV-1-associated neurocognitive disorders (HAND) continue to be diagnosed in patients with HIV-1 undergoing treatment. The extensive clinical manifestations of HAND include behavioral, cognitive, and motor dysfunctions that severely affect the patients’ quality of life. The pathogenesis of HAND has received increasing attention as a potential avenue by which to improve the treatment of the condition. Many studies have shown that endoplasmic reticulum (ER) stress, autophagy, and their interaction play important roles in the onset and development of neurodegenerative diseases. While the accumulation of misfolded proteins can induce ER stress, autophagy can effectively remove accumulated toxic proteins, reduce ER stress, and thus inhibit the development of neuropathy. Through the in-depth study of ER stress and autophagy, both have been recognized as promising targets for pharmacotherapeutic intervention in the treatment of HAND. This review will highlight the effects of ER stress, autophagy, and their interaction in the context of HAND, thereby helping to inform the future development of targeted treatments for patients with HAND.

Abbas W, Khan KA, Tripathy MK, Dichamp I, Keita M, Rohr O et al (2012) Inhibition of ER stress-mediated apoptosis in macrophages by nuclear-cytoplasmic relocalization of eEF1A by the HIV-1 Nef protein. Cell Death Dis 3(4)

Adolph TE, Tomczak MF, Niederreiter N, Ko HJ, Böck J, Martinez-Naves E et al (2013) Paneth cells as a site of origin for intestinal inflammation. Nature 503(7475):272–276PubMedPubMedCentral

Akay C, Lindl KA, Shyam N, Nabet B, Geonaga-Vazquez Y, Ruzbarsky J, Wang Y, Kolson DL, Jordan-Sciutto KL (2012) Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND). Neuropathol Appl Neurobiol 38(2):175–200PubMedPubMedCentral

Alirezaei M, Kiosses WB, Fox HS (2008a) Decreased neuronal autophagy in HIV dementia. Autophagy

Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS (2008b) Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS One 3(8)

Anderson ER, Zink WE, Xiong H, Gendelman HE (2002) HIV-1-associated dementia: a metabolic encephalopathy perpetrated by virus-infected and immune-competent mononuclear phagocytes. J Acquir Immune Defic Syndr 31:43–54

András IE, Toborek MJIL (2013) Amyloid beta accumulation in HIV-1-infected brain: the role of the blood brain barrier. IUBMB Life 65(1):43–49PubMed

Bahr BA, Bendiske J (2002) The neuropathogenic contributions of lysosomal dysfunction. J Neurochem 83(3):481–489PubMed

Bednarczyk M, Zmarzly N, Grabarek B, Mazurek U, Mucwierzgon M (2018) Genes involved in the regulation of different types of autophagy and their participation in cancer pathogenesis. Oncotarget 9(76):34413–34428PubMedPubMedCentral

Cai Y, Arikkath J, Yang L, Guo M-L, Periyasamy P, Buch SJA (2016) Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy 12(2):225–244PubMedPubMedCentral

Carvalho C, Santos MS, Oliveira CR, Moreira PI (2015) Alzheimer\’s disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers. Biochim Biophys Acta 1852(8):1665–1675PubMed

Castrogonzalez S, Shi Y, Colomerlluch M, Song Y, Mowery K, Almodovar S et al (2020) HIV-1 Nef counteracts autophagy restriction by enhancing the association between BECN1 and its inhibitor BCL2 in a PRKN-dependent manner. Autophagy:1–25

Churchill MJ, Deeks SG, Margolis DM, Siliciano RF, Swanstrom R (2016) HIV reservoirs: what, where and how to target them. Nat Rev Microbiol 14(1):55–60PubMed

Conway O, Akpinar HA, Rogov VV, Kirkin V (2019) Selective autophagy receptors in neuronal health and disease. J Mol Biol

Cornejo VCH, Hetz C (2013) The unfolded protein response in Alzheimer’s disease. Semin Immunopathol 35(3):277–292PubMed

Crews L, Spencer B, Desplats P, Patrick C, Paulino A, Rockenstein E et al (2010) Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of α-synucleinopathy. PLoS One (2):5

Dandekar A, Mendez R, Zhang K (2015) Cross talk between ER stress, oxidative stress, and Inflammation in health and disease. Methods Mol Biol 1292:205–214PubMed

Deegan S, Koryga I, Glynn S, Gupta S, Gorman A, Samali A (2014) A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy. Biochem Biophys Res Commun 456

Deng Z, Purtell K, Lachance V, Wold MS, Chen S, Yue Z (2017) Autophagy receptors and neurodegenerative diseases. Trends Cell Biol 27(7):491–504PubMed

Díaz-Hung M-L, Martínez G, Hetz C (2020) Chapter two - emerging roles of the unfolded protein response (UPR) in the nervous system: a link with adaptive behavior to environmental stress? In: Kepp O, Galluzzi L (eds) International Review of Cell and Molecular Biology. Academic Press, pp 29–61

Djajadikerta A, Keshri S, Pavel M, Prestil R, Ryan L, Rubinsztein DC (2019) Autophagy induction as a therapeutic strategy for neurodegenerative diseases. J Mol Biol

Djajadikerta A, Keshri S, Pavel M, Prestil R, Ryan L, Rubinsztein D (2020) Autophagy induction as a therapeutic strategy for neurodegenerative diseases. J Mol Biol 432(8):2799–2821PubMed

Edinger AL, Thompson CB (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16(6):663–669PubMed

Fan Y, He JJ (2016) HIV-1 tat induces unfolded protein response and endoplasmic reticulum stress in astrocytes and causes neurotoxicity through glial Fibrillary acidic protein (GFAP) activation and aggregation. J Biol Chem 291(43):22819–22829PubMedPubMedCentral

Fields J, Dumaop W, Elueteri S, Campos S, Serger E, Trejo M, Kosberg K, Adame A, Spencer B, Rockenstein E, He JJ, Masliah E (2015) HIV-1 tat alters neuronal autophagy by modulating autophagosome fusion to the lysosome: implications for HIV-associated neurocognitive disorders. J Neurosci 35(5):1921–1938PubMedPubMedCentral

Foster JL, Garcia JV (2008) HIV-1 Nef: at the crossroads. Retrovirology 5(1):84–84PubMedPubMedCentral

Galleguillos D, Matus S, Valenzuela V, Valdés P, Martinez A, Nassif M, et al. (2009) Targeting endoplasmic reticulum stress pathways to treat neurological disorders associated with protein misfolding. Protein Misfolding Disorders: A Trip into the ER

González-Scarano F, Martín-García J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5(1):69–81PubMed

Guo ML, Liao K, Periyasamy P, Yang L, Cai Y, Callen SE, Buch S (2015) Cocaine-mediated microglial activation involves the ER stress-autophagy axis. Autophagy 11(7):995–1009PubMedPubMedCentral

Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889PubMed

Hetz CA, Medicine CSJCM (2006) Emerging roles of the unfolded protein response signaling in physiology and disease. Curr Mol Med 6(1):1–3PubMed

Høyer-Hansen M, Jäättelä M (2007) Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ 14(9):1576–1582PubMed

Jones GJ, Barsby NL, Cohen EA, Holden J, Harris K, Dickie P, Jhamandas J, Power C (2007) HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration. J Neurosci 27(14):3703–3711PubMedPubMedCentral

Kanmogne GD, Schall K, Leibhart J, Knipe B, Gendelman HE, Persidsky Y (2006) HIV-1 gp120 compromises blood–brain barrier integrity and enhance monocyte migration across blood–brain barrier: implication for viral neuropathogenesis. J Cereb Blood Flow Metab 27(1):123–134PubMed

Karsli-Uzunbas G, Guo JY, Price S, Teng X, Laddha SV, Khor S, Kalaany NY, Jacks T, Chan CS, Rabinowitz JD, White E (2014) Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov 4(8):914–927PubMedPubMedCentral

Kaushik S, Cuervo AMJNM (2015) Proteostasis and aging. Nature 21(12):1406–1415

Kim I, Xu W, Reed JCJNRDD (2008) Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov 7(12):1013–1030PubMed

Kirchhoff F (2010) Immune evasion and counteraction of restriction factors by HIV-1 and other primate Lentiviruses. Cell Host Microbe 8(1):55–67PubMed

Kishi T, Matsunaga S, Oya K, Nomura I, Ikuta T, Iwata N (2017) Memantine for Alzheimer's disease: an updated systematic review and meta-analysis. J Alzheimers Dis 60(2):401–425PubMed

Komatsu M, Waguri S, Chiba T, Murata S, Iwata J-I, Tanida I et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441(7095):880–884PubMed

Kouroku Y, Fujita E, Tanida I (2007) ER stress (PERK|[sol]|eIF2|[alpha]| phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ 14(2):230–239PubMed

Kragh CL, Ubhi K, Wyss-Corey T, Masliah EJBP (2012) Autophagy in dementias. Brain Pathol 22(1):99–109PubMed

Kroemer G, Jäättelä M (2005) Lysosomes and autophagy in cell death control. Nat Rev Cancer 5(11):886–897PubMed

Kumar YR, Soo-Wan C, Hyung-Ryong K, Chae HJ (2014) Endoplasmic reticulum stress and cancer. J Cancer Prevent 19(2):75–88

Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A, Federico M, Panganiban A, Vergne I, Deretic V (2009) Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186(2):255–268PubMedPubMedCentral

Levine BJC (2005) Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120(2):159–162PubMed

Li Y, Guo Y, Yu X, Duan W, Hong K et al (2015) Trehalose decreases mutant sod1 expression and alleviates motor deficiency in early but not end-stage amyotrophic lateral sclerosis in a SOD1-G93A mouse model. Neuroscience

Ligon C, Cai Y, Buch S, Arikkath J (2020) A selective role for a component of the autophagy pathway in coupling the Golgi apparatus to dendrite polarity in pyramidal neurons. Neurosci Lett 730:135048PubMed

Lindholm D, Wootz H, Korhonen LJCD (2006) Differentiation. ER stress and neurodegenerative diseases. Cell Death Differ 13(3):385–392PubMed

Liu S, Xing Y, Wang J, Pan R, Li G, Tang H, Chen G, Yan L, Guo L, Jiang M, Gong Z, Lin L, Dong J (2019) The dual role of HIV-1 gp120 V3 loop-induced autophagy in the survival and apoptosis of the primary rat hippocampal neurons. Neurochem Res 44(7):1636–1652PubMed

Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8(9):741–752PubMed

Matus S, Lisbona F, Torres M, Leon C, Thielen P, Hetz CJCMM (2008) The stress rheostat: an interplay between the unfolded protein response (UPR) and autophagy in Neurodegeneration. Curr Mol Med 8(3):157–172PubMed

Meco AD, Curtis ME, Lauretti E, Pratico D (2019) Autophagy dysfunction in Alzheimer’s disease: mechanistic insights and new therapeutic opportunities. Biol Psychiatry

Mehrbod P, Ande SR, Alizadeh J, Rahimizadeh S, Shariati A, Malek H, Hashemi M, Glover KKM, Sher AA, Coombs KM, Ghavami S (2019) The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections. Virulence 10(1):376–413PubMedPubMedCentral

Menzies FM, Fleming A, Rubinsztein DC (2015) Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci 16(6):345–357PubMed

Menzies FM, Fleming A, Caricasole A, Bento CF, Andrews SP, Ashkenazi A, Füllgrabe J, Jackson A, Jimenez Sanchez M, Karabiyik C, Licitra F, Lopez Ramirez A, Pavel M, Puri C, Renna M, Ricketts T, Schlotawa L, Vicinanza M, Won H, Zhu Y, Skidmore J, Rubinsztein DC (2017) Autophagy and Neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron 93(5):1015–1034PubMed

Meulendyke KA, Croteau JD, Zink MC (2014) HIV life cycle, innate immunity and autophagy in the central nervous system. Curr Opin HIV AIDS 9(6):565–571PubMedPubMedCentral

Mizushima N, Komatsu MJC (2011) Autophagy: renovation of cells and tissues. Cell 147(4):728–741PubMed

Nah J, Yuan J, Jung Y (2015) Autophagy in neurodegenerative diseases: from mechanism to therapeutic approach. Mol Cell 38(5):381–389

Nakamura S, Yoshimori T (2017) New insights into autophagosome–lysosome fusion. J Cell Sci 130(7):1209–1216PubMed

Nardacci R, Ciccosanti F, Marsella C, Ippolito G, Piacentini M, Fimia GM (2017) Role of autophagy in HIV infection and pathogenesis. J Intern Med 281(5):422–432PubMed

Nie T, Yang S, Ma H, Zhang L, Lu F, Tao K, Wang R, Yang R, Huang L, Mao Z, Yang Q (2016) Regulation of ER stress-induced autophagy by GSK3β-TIP60-ULK1 pathway. Cell Death Dis 7(12):e2563PubMedPubMedCentral

Norman JP, Perry SW, Reynolds HM, Michelle K, De MBKL, Margarita T et al (2008) HIV-1 Tat activates neuronal ryanodine receptors with rapid induction of the unfolded protein response and mitochondrial hyperpolarization. PLoS One 3(11):e3731PubMedPubMedCentral

Ogata M, Hino SI, Saito A, Morikawa K, Molecular KIJ, Biology C (2007) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26(24):9220–9231

Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith R, Görgün CZ, Hotamisligil GS (2006) Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313(5790):1137–1140PubMedPubMedCentral

Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O'Kane CJ, Rubinsztein DC (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36(6):585–595PubMed

Rawat P, Teodorofdiedrich C, Spector SA (2019) Human immunodeficiency virus type-1 single-stranded RNA activates the NLRP3 inflammasome and impairs autophagic clearance of damaged mitochondria in human microglia. Glia 67(5):802–824PubMed

Rempel HC, Lynn PJA (2005) HIV-1 tat inhibits neprilysin and elevates amyloid beta. AIds 25(2):S460–S461

Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. Aids 21(14):1915–1921PubMed

Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529PubMed

Roussel BD, Kruppa AJ, Miranda E, Crowther DC, Lomas DA, Marciniak SJJLN (2013) Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol 12(1):105–118PubMed

Sarkar S, Floto RA, Berger Z, Imarisio S, Cordenier A, Pasco M, Cook LJ, Rubinsztein DC (2005) Lithium induces autophagy by inhibiting inositol Monophosphatase. J Cell Biol 170(7):1101–1111PubMedPubMedCentral

Schaeffer V, Lavenir I, Ozcelik S, Tolnay M, Winkler DT, Goedert MJB (2012) Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain J Neurol 135(7):2169–2177

Scheper W, Hoozemans JJM (2015) The unfolded protein response in neurodegenerative diseases: a neuropathological perspective. Acta Neuropathol 130(3):315–331PubMedPubMedCentral

Shah A, Kumar A (2010) HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-κB pathway and can be silenced by gp120-specific siRNA. J Neuroinflammation 7(1):96PubMedPubMedCentral

Shah A, Vaidya NK, Bhat HK, Kumar A (2016) HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK and AP-1 pathway. Sci Rep 6:18929PubMedPubMedCentral

Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J (2006) Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem 281(20):14474–14485PubMed

Son JH, Shim JH, Kim KH, Ha JY, Han JY (2012) Neuronal autophagy and neurodegenerative diseases. Exp Mol Med 44(2):89–98PubMedPubMedCentral

Tabas I, Ron DJNCB (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13(3):184–190PubMedPubMedCentral

Takahama M, Akira S, Saitoh T (2018) Autophagy limits activation of the inflammasomes. Immunol Rev 281(1):62–73PubMed

Tewari M, Monika, Varghese RK, Menon M, Seth P (2015) Astrocytes mediate HIV-1 tat-induced neuronal damage via ligand-gated ion channel P2X7R. J Neurochem 132(4):464–476PubMed

Thangaraj A, Sil S, Tripathi A, Chivero ET, Periyasamy P, Buch S (2020) Targeting endoplasmic reticulum stress and autophagy as therapeutic approaches for neurological diseases. Int Rev Cell Mol Biol:350

Ton HT, Xiong H (2013) Astrocyte dysfunctions and HIV-1 neurotoxicity. J AIDS Clin Res 4(11):255–255PubMedPubMedCentral

Upton JP, Austgen K, Nishino M, Coakley KM, Hagen A, Han D, Papa FR, Oakes SA (2008) Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol 28(12):3943–3951PubMedPubMedCentral

Vallejo-Gracia A, Chen I, Perrone R, Besnard E, Boehm D, Battivelli E et al (2020) FOXO1 promotes HIV latency by suppressing ER stress in T cells. Nat Microbiol 5:1144–1157PubMedPubMedCentral

Walter P, Ron DJS (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334(6059):1081–1086PubMed

Wang I, Tsai KJ, Shen CK (2015) Autophagy activators rescue and alleviate the pathogenesis of a FTLD-TDP model with TDP-43 Proteinopathies (S8.005)

Wang Y, Liu F, Wang Y, Guan R, Chen C, Li D et al (2018) Autophagic modulation by Trehalose reduces accumulation of TDP-43 in a cell model of amyotrophic lateral sclerosis via TFEB activation. Neurotox Res 34(1):109–120PubMed

Wong YC, Holzbaur ELF (2014) Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci 111(42):E4439–E4448PubMedPubMedCentral

Wu X, Dong H, Ye X, Zhong L, Cao T, Xu Q, Wang J, Zhang Y, Xu J, Wang W, Wei Q, Liu Y, Wang S, Shao Y, Xing H (2018) HIV-1 tat increases BAG3 via NF-κB signaling to induce autophagy during HIV-associated neurocognitive disorder. Cell Cycle 17(13):1614–1623PubMedPubMedCentral

Yeganeh B, Jäger R, Gorman AM, Samali A, Ghavami S (2015) Induction of autophagy: role of endoplasmic reticulum stress and unfolded protein response. In: Hayat MA (ed) Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging. Academic Press, Amsterdam, pp 91–101

Yoon S-Y, Kim D-H (2016) Alzheimer's disease genes and autophagy. Brain Res 1649:201–209PubMed

Yoriko K, Eriko F, Atsushi J (2002) Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation. Hum Mol Genet 13:13

Yu J, Nagasu H, Murakami T, Hoang H, Broderick L, Hoffman HM, Horng T (2014) Inflammasome activation leads to Caspase-1–dependent mitochondrial damage and block of mitophagy. Proc Natl Acad Sci U S A 111(43):15514–15519PubMedPubMedCentral

Zhang X, Xin H, Li T, Li L, Le W (2011) Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model. J Alzheimers Dis Jad 24(4):739–749PubMed

Zhao L, Longo-Guess C, Harris BS, Lee JW, Ackerman SLJNG (2005) Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP. Nat Genet 37(9):974–979PubMed

Zhou BY, Liu Y, Kim BO, Xiao Y, He JJ (2004) Astrocyte activation and dysfunction and neuron death by HIV-1 tat expression in astrocytes. Mol Cell Neurosci 27(3):296–305PubMed

Zhou D, Eliezer M, Spector SA (2011) Autophagy is increased in postmortem brains of persons with HIV-1-associated encephalitis. J Infect Dis 11:11

Title: Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders
Authors: Xue Chen
Tong Zhang
Yulin Zhang
Publication date: 01-12-2020
Publisher: Springer International Publishing
Keywords: Alzheimer's Disease
Human Immunodeficiency Virus
Targeted Therapy
Alzheimer's Disease
Published in: Journal of NeuroVirology / Issue 6/2020
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-020-00906-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2020

Novel method to quantify phenotypic markers of HIV-associated neurocognitive disorder in a murine SCID model

Status of humoral and cellular immune markers in human T-cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers in northeastern Iran, Mashhad

The University of California San Diego performance-based skills assessment: a useful tool to detect mild everyday functioning difficulties in HIV-infected patients with very good immunological condition

Studying the neuropsychological sequelae of SARS-CoV-2: lessons learned from 35 years of neuroHIV research

Middle cerebral artery ischemic stroke and COVID-19: a case report

Progressive multifocal leukoencephalopathy in an HIV patient was diagnosed by 3 times lumbar punctures and 2 times brain biopsies