Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300

Authors: Feng Zhou, Xiaomei Liu, Dongjiao Zuo, Min Xue, Lin Gao, Ying Yang, Jing Wang, Liping Niu, Qianwen Cao, Xiangyang Li, Hui Hua, Bo Zhang, Minmin Hu, Dianshuai Gao, Kuiyang Zheng, Yoshihiro Izumiya, Renxian Tang

Published in: Journal of Neuroinflammation | Issue 1/2018

Login to get access

Abstract

Background

HIV-associated neurocognitive disorder (HAND) is a neurodegenerative disease associated with persistent neuroinflammation and subsequent neuron damage. Pro-inflammatory factors and neurotoxins from activated astrocytes by HIV-1 itself and its encoded proteins, including the negative factor (Nef), are involved in the pathogenesis of HAND. This study was designed to find potential lncRNAs that regulate astrocyte functions and inflammation process.

Methods

We performed microarray analysis of lncRNAs from primary mouse astrocytes treated with Nef protein. Top ten lncRNAs were validated through real-time PCR analysis. Gene ontology (GO) and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. RIP and ChIP assays were performed to demonstrate the mechanism of lncRNA regulating gene expression.

Results

There were 638 co-upregulated lncRNAs and 372 co-downregulated lncRNAs in primary astrocytes treated with Nef protein for both 6 h and 12 h. GO and KEGG pathway analysis showed that the biological functions of top differential-expressed mRNAs were associated with inflammatory cytokines and chemokine. Knockdown of lncRNA AK006025, not AK138360, inhibited significantly CXCL9, CXCL10 (IP-10), and CXCL11 expression in astrocytes treated with Nef protein. Mechanism study showed that AK006025 associated with CBP/P300 was enriched in the promoter of CXCL9, CXCL10, and CXCL11 genes.

Conclusions

Our findings uncovered the expression profiles of lncRNAs and mRNAs in vitro, which might help to understand the pathways that regulate astrocyte activation during the process of HAND.
Appendix
Available only for authorised users
Literature
1.
Clifford DB, Ances BM. HIV-associated neurocognitive disorder. Lancet Infect Dis. 2013;13(11):976–86.CrossRef
2.
Ghafouri M, Amini S, Khalili K, Sawaya BE. HIV-1 associated dementia: symptoms and causes. Retrovirology. 2006;3:28.CrossRef
3.
Gaskill PJ, Miller DR, Gamble-George J, Yano H, Khoshbouei H. HIV, Tat and dopamine transmission. Neurobiol Dis. 2017;105:51–73.CrossRef
4.
Gonzalez E, Rovin BH, Sen L, Cooke G, Dhanda R, Mummidi S, Kulkarni H, Bamshad MJ, Telles V, Anderson SA, et al. HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci U S A. 2002;99(21):13795–800.CrossRef
5.
Huang Y, Zhao L, Jia B, Wu L, Li Y, Curthoys N, Zheng JC. Glutaminase dysregulation in HIV-1-infected human microglia mediates neurotoxicity: relevant to HIV-1-associated neurocognitive disorders. J Neurosci. 2011;31(42):15195–204.CrossRef
6.
Spudich S. HIV and neurocognitive dysfunction. Curr HIV/AIDS Rep. 2013;10(3):235–43.CrossRef
7.
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.CrossRef
8.
Xu C, Liu J, Chen L, Liang S, Fujii N, Tamamura H, Xiong H. HIV-1 gp120 enhances outward potassium current via CXCR4 and cAMP-dependent protein kinase a signaling in cultured rat microglia. Glia. 2011;59(6):997–1007.CrossRef
9.
Shah A, Kumar A. HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-kappaB pathway and can be silenced by gp120-specific siRNA. J Neuroinflammation. 2010;7:96.CrossRef
10.
Wyss-Coray T, Masliah E, Toggas SM, Rockenstein EM, Brooker MJ, Lee HS, Mucke L. Dysregulation of signal transduction pathways as a potential mechanism of nervous system alterations in HIV-1 gp120 transgenic mice and humans with HIV-1 encephalitis. J Clin Invest. 1996;97(3):789–98.CrossRef
11.
Green MV, Thayer SA. NMDARs adapt to neurotoxic HIV protein Tat downstream of a GluN2A-ubiquitin ligase signaling pathway. J Neurosci. 2016;36(50):12640–9.CrossRef
12.
Bruce-Keller AJ, Chauhan A, Dimayuga FO, Gee J, Keller JN, Nath A. Synaptic transport of human immunodeficiency virus-tat protein causes neurotoxicity and gliosis in rat brain. J Neurosci. 2003;23(23):8417–22.CrossRef
13.
D'Aversa TG, Yu KO, Berman JW. Expression of chemokine by human fetal microglia after treatment with the human immunodeficiency virus type 1 protein Tat. J Neuro-Oncol. 2004;10(2):86–97.
14.
Kim BO, Liu Y, Ruan Y, Xu ZC, Schantz L, He JJ. Neuropathologies in transgenic mice expressing human immunodeficiency virus type 1 Tat protein under the regulation of the astrocyte-specific glial fibrillary acidic protein promoter and doxycycline. Am J Pathol. 2003;162(5):1693–707.CrossRef
15.
Bergonzini V, Calistri A, Salata C, Del Vecchio C, Sartori E, Parolin C, Palu G. Nef and cell signaling transduction: a possible involvement in the pathogenesis of human immunodeficiency virus-associated dementia. J Neuro-Oncol. 2009;15(3):238–48.
16.
Liu X, Shah A, Gangwani MR, Silverstein PS, Fu M, Kumar A. HIV-1 Nef induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors. Sci Rep. 2014;4:4450.CrossRef
17.
Hong S, Banks WA. Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications. Brain Behav Immun. 2015;45:1–12.CrossRef
18.
Allen NJ, Barres BA. Neuroscience: glia - more than just brain glue. Nature. 2009;457(7230):675–7.CrossRef
19.
Barres BA. The mystery and magic of glia: a perspective on their roles in health and disease. Neuron. 2008;60(3):430–40.CrossRef
20.
Wilson EH, Weninger W, Hunter CA. Trafficking of immune cells in the central nervous system. J Clin Invest. 2010;120(5):1368–79.CrossRef
21.
Budka H, Wiley CA, Kleihues P, Artigas J, Asbury AK, Cho ES, Cornblath DR, Dal Canto MC, DeGirolami U, Dickson D, et al. HIV-associated disease of the nervous system: review of nomenclature and proposal for neuropathology-based terminology. Brain Pathol. 1991;1(3):143–52.CrossRef
22.
Kestler HW 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991;65(4):651–62.CrossRef
23.
Puzar Dominkus P, Ferdin J, Plemenitas A, Peterlin BM, Lenassi M. Nef is secreted in exosomes from Nef.GFP-expressing and HIV-1-infected human astrocytes. J Neuro-Oncol. 2017;23(5):713–24.
24.
Khan MB, Lang MJ, Huang MB, Raymond A, Bond VC, Shiramizu B, Powell MD. Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Abeta(1-42) secretion in SH-SY5Y neural cells. J Neuro-Oncol. 2016;22(2):179–90.
25.
van Marle G, Henry S, Todoruk T, Sullivan A, Silva C, Rourke SB, Holden J, McArthur JC, Gill MJ, Power C. Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10. Virology. 2004;329(2):302–18.CrossRef
26.
Chompre G, Cruz E, Maldonado L, Rivera-Amill V, Porter JT, Noel RJ, Jr. Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory. Neurobiol Dis 2013; 49:128–136.CrossRef
27.
Torres-Munoz J, Stockton P, Tacoronte N, Roberts B, Maronpot RR, Petito CK. Detection of HIV-1 gene sequences in hippocampal neurons isolated from postmortem AIDS brains by laser capture microdissection. J Neuropathol Exp Neurol. 2001;60(9):885–92.CrossRef
28.
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.CrossRef
29.
Qureshi IA, Mehler MF. Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci. 2012;13(8):528–41.CrossRef
30.
Johnson R. Long non-coding RNAs in Huntington's disease neurodegeneration. Neurobiol Dis. 2012;46(2):245–54.CrossRef
31.
Roberts TC, Morris KV, Wood MJ. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease. Philos Trans R Soc Lond Ser B Biol Sci. 2014;369(1652).CrossRef
32.
Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, Becker-Santos DD, MacAulay CE, Lam S, Brown CJ, Lam WL. Human cancer long non-coding RNA transcriptomes. PLoS One. 2011;6(10):e25915.CrossRef
33.
Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–72.CrossRef
34.
Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477(7364):295–300.CrossRef
35.
Wang J, Zhao H, Fan Z, Li G, Ma Q, Tao Z, Wang R, Feng J, Luo Y, Long Noncoding RNA. H19 promotes neuroinflammation in ischemic stroke by driving histone deacetylase 1-dependent M1 microglial polarization. Stroke. 2017;48(8):2211–21.CrossRef
36.
NE II, Heward JA, Roux B, Tsitsiou E, Fenwick PS, Lenzi L, Goodhead I, Hertz-Fowler C, Heger A, Hall N, et al. Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes. Nat Commun. 2014;5:3979.CrossRef
37.
Zhou X, Han X, Wittfeldt A, Sun J, Liu C, Wang X, Gan LM, Cao H, Liang Z. Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-kappaB pathway. RNA Biol. 2016;13(1):98–108.CrossRef
38.
Zhao G, Su Z, Song D, Mao Y, Mao X. The long noncoding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-kappaB. FEBS Lett. 2016;590(17):2884–95.CrossRef
39.
Zhang F, Wu L, Qian J, Qu B, Xia S, La T, Wu Y, Ma J, Zeng J, Guo Q, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016;75:96–104.CrossRef
40.
Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, Berger SL. Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell. 2001;8(6):1243–54.CrossRef
41.
Schroder S, Herker E, Itzen F, He D, Thomas S, Gilchrist DA, Kaehlcke K, Cho S, Pollard KS, Capra JA, et al. Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells. Mol Cell. 2013;52(3):314–24.CrossRef
42.
Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V, Zlobin A, Diaz MO, Scacheri PC, Harte PJ. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development. 2009;136(18):3131–41.CrossRef
43.
Wang F, Marshall CB, Ikura M. Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition. Cell Mol Life Sci. 2013;70(21):3989–4008.CrossRef
44.
Bedford DC, Kasper LH, Fukuyama T, Brindle PK. Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases. Epigenetics. 2010;5(1):9–15.CrossRef
45.
Jin Q, Yu LR, Wang L, Zhang Z, Kasper LH, Lee JE, Wang C, Brindle PK, Dent SY, Ge K. Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J. 2011;30(2):249–62.CrossRef
46.
Bose DA, Donahue G, Reinberg D, Shiekhattar R, Bonasio R, Berger SL. RNA binding to CBP stimulates histone acetylation and transcription. Cell. 2017;168(1–2):135–49 e22.CrossRef
47.
Cui W, Yoneda R, Ueda N, Kurokawa R. Arginine methylation of translocated in liposarcoma (TLS) inhibits its binding to long noncoding RNA, abrogating TLS-mediated repression of CBP/p300 activity. J Biol Chem. 2018;293(28):10937–48.CrossRef
48.
Liu XM, He FX, Pang RR, Zhao D, Qiu W, Shan K, Zhang J, Lu YL, Li Y, Wang YW. Interleukin-17 (IL-17)-induced microRNA 873 (miR-873) contributes to the pathogenesis of experimental autoimmune encephalomyelitis by targeting A20 ubiquitin-editing enzyme. J Biol Chem. 2014;289(42):28971–86.CrossRef
49.
Liu X, Zhang Q, Wang W, Zuo D, Wang J, Zhou F, Niu L, Li X, Qin S, Kou Y, et al. Analysis of long noncoding RNA and mRNA expression profiles in IL-9-activated astrocytes and EAE mice. Cell Physiol Biochem. 2018;45(5):1986–98.CrossRef
50.
Kang Z, Altuntas CZ, Gulen MF, Liu C, Giltiay N, Qin H, Liu L, Qian W, Ransohoff RM, Bergmann C, et al. Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis. Immunity. 2010;32(3):414–25.CrossRef
51.
Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329(5992):689–93.CrossRef
52.
Zhou F, Shimoda M, Olney L, Lyu Y, Tran K, Jiang G, Nakano K, Davis RR, Tepper CG, Maverakis E, et al. Oncolytic reactivation of KSHV as a therapeutic approach for primary effusion lymphoma. Mol Cancer Ther. 2017;16(11):2627–38.CrossRef
53.
Raymond AD, Campbell-Sims TC, Khan M, Lang M, Huang MB, Bond VC, Powell MD. HIV type 1 Nef is released from infected cells in CD45(+) microvesicles and is present in the plasma of HIV-infected individuals. AIDS Res Hum Retrovir. 2011;27(2):167–78.CrossRef
54.
Cullen BR. HIV-1 auxiliary proteins: making connections in a dying cell. Cell. 1998;93(5):685–92.CrossRef
55.
Fujii Y, Otake K, Tashiro M, Adachi A. Soluble Nef antigen of HIV-1 is cytotoxic for human CD4+ T cells. FEBS Lett. 1996;393(1):93–6.CrossRef
56.
Qiao X, He B, Chiu A, Knowles DM, Chadburn A, Cerutti A. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. Nat Immunol. 2006;7(3):302–10.CrossRef
57.
Yan Q, Ma X, Shen C, Cao X, Feng N, Qin D, Zeng Y, Zhu J, Gao SJ, Lu C. Inhibition of Kaposi's sarcoma-associated herpesvirus lytic replication by HIV-1 Nef and cellular microRNA hsa-miR-1258. J Virol. 2014;88(9):4987–5000.CrossRef
58.
Marecki JC, Cool CD, Parr JE, Beckey VE, Luciw PA, Tarantal AF, Carville A, Shannon RP, Cota-Gomez A, Tuder RM, et al. HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques. Am J Respir Crit Care Med. 2006;174(4):437–45.CrossRef
59.
Xue M, Yao S, Hu M, Li W, Hao T, Zhou F, Zhu X, Lu H, Qin D, Yan Q, et al. HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway. Nucleic Acids Res. 2014;42(15):9862–79.CrossRef
60.
Narasipura SD, Kim S, Al-Harthi L. Epigenetic regulation of HIV-1 latency in astrocytes. J Virol. 2014;88(5):3031–8.CrossRef
61.
Prensner JR, Iyer MK, Sahu A, Asangani IA, Cao Q, Patel L, Vergara IA, Davicioni E, Erho N, Ghadessi M, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet. 2013;45(11):1392–8.CrossRef
62.
Ogawa N, Ping L, Zhenjun L, Takada Y, Sugai S. Involvement of the interferon-gamma-induced T cell-attracting chemokine, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjogren's syndrome. Arthritis Rheum. 2002;46(10):2730–41.CrossRef
Metadata
Title
HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300
Authors
Feng Zhou
Xiaomei Liu
Dongjiao Zuo
Min Xue
Lin Gao
Ying Yang
Jing Wang
Liping Niu
Qianwen Cao
Xiangyang Li
Hui Hua
Bo Zhang
Minmin Hu
Dianshuai Gao
Kuiyang Zheng
Yoshihiro Izumiya
Renxian Tang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1343-x

Other articles of this Issue 1/2018

Journal of Neuroinflammation 1/2018 Go to the issue

Research

Anti-high mobility group box 1 antibody suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury

Research

Cytokine alterations in first-episode schizophrenia and bipolar disorder: relationships to brain structure and symptoms

Research

Necrotizing enterocolitis is associated with acute brain responses in preterm pigs

Letter to the Editor

NLRP3 inflammasome-dependent pyroptosis is proposed to be involved in the mechanism of age-dependent isoflurane-induced cognitive impairment

Research

Lentivirus-mediated overexpression of OTULIN ameliorates microglia activation and neuroinflammation by depressing the activation of the NF-κB signaling pathway in cerebral ischemia/reperfusion rats

Research

The plasticity of primary microglia and their multifaceted effects on endogenous neural stem cells in vitro and in vivo