Investigating HIV-Human Interaction Networks to Unravel Pathogenic Mechanism for Drug Discovery: A Systems Biology Approach

Author(s): Cheng-Wei Li, Bor-Sen Chen*.

Journal Name: Current HIV Research

Volume 16 , Issue 1 , 2018

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Two big issues in the study of pathogens are determining how pathogens infect hosts and how the host defends itself against infection. Therefore, investigating host-pathogen interactions is important for understanding pathogenicity and host defensive mechanisms and treating infections.

Methods: In this study, we used omics data, including time-course data from high-throughput sequencing, real-time polymerase chain reaction, and human microRNA (miRNA) and protein-protein interaction to construct an interspecies protein-protein and miRNA interaction (PPMI) network of human CD4+ T cells during HIV-1 infection through system modeling and identification.

Results: By applying a functional annotation tool to the identified PPMI network at each stage of HIV infection, we found that repressions of three miRNAs, miR-140-5p, miR-320a, and miR-941, are involved in the development of autoimmune disorders, tumor proliferation, and the pathogenesis of T cells at the reverse transcription stage. Repressions of miR-331-3p and miR-320a are involved in HIV-1 replication, replicative spread, anti-apoptosis, cell proliferation, and dysregulation of cell cycle control at the integration/replication stage. Repression of miR-341-5p is involved in carcinogenesis at the late stage of HIV-1 infection.

Conclusion: By investigating the common core proteins and changes in specific proteins in the PPMI network between the stages of HIV-1 infection, we obtained pathogenic insights into the functional core modules and identified potential drug combinations for treating patients with HIV-1 infection, including thalidomide, oxaprozin, and metformin, at the reverse transcription stage; quercetin, nifedipine, and fenbendazole, at the integration/replication stage; and staurosporine, quercetin, prednisolone, and flufenamic acid, at the late stage.

Keywords: HIV, miRNA, AIDS, Interspecies protein-protein miRNA interaction network, Host-pathogen interaction network, Multiple drug.

[1]
Jansen CA, Piriou E, De Cuyper IM, et al. Long-term highly active antiretroviral therapy in chronic HIV-1 infection: evidence for reconstitution of antiviral immunity. Antiviral Ther 2006; 11(1): 105-16.
[2]
Perelson AS. Modelling viral and immune system dynamics. Nat Rev Immunol 2002; 2(1): 28-36.
[3]
Duskova K, Nagilla P, Le HS, et al. MicroRNA regulation and its effects on cellular transcriptome in Human Immunodeficiency Virus-1 (HIV-1) infected individuals with distinct viral load and CD4 cell counts. BMC Infect Dis 2013; 13.
[4]
Chen BS, Li CW. Constructing an integrated genetic and epigenetic cellular network for whole cellular mechanism using high-throughput next-generation sequencing data. BMC Syst Biol 2016; 10(1): 18.
[5]
Sun GH, Li HT, Wu XW, et al. Interplay between HIV-1 infection and host microRNAs. Nucleic Acids Res 2012; 40(5): 2181-96.
[6]
Whisnant AW, Bogerd HP, Flores O, et al. In-Depth Analysis of the Interaction of HIV-1 with Cellular microRNA Biogenesis and Effector Mechanisms. Mbio 2013; 4(2): e00193-13.
[7]
Mohammadi P, Desfarges S, Bartha I, et al. 24 Hours in the Life of HIV-1 in a T Cell Line. Plos Pathogens 2013; 9(1)
[8]
Lu J, Clark AG. Impact of microRNA regulation on variation in human gene expression. Genome Res 2012; 22(7): 1243-54.
[9]
Li CW, Wang WH, Chen BS. Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells. Oncotarget 2016.
[10]
Keshet I, Yisraeli J, Cedar H. Effect of regional DNA methylation on gene expression. Proc Natl Acad Sci USA 1985; 82(9): 2560-4.
[11]
Li C-W, Chen B-S. Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data. Dis Markers 2016; 2016: 4149608.
[12]
O’Doherty U, Swiggard WJ, Malim MH. Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol 2000; 74(21): 10074-80.
[13]
Hsu CW, Juan HF, Huang HC. Characterization of microRNA-regulated protein-protein interaction network. Proteomics 2008; 8(10): 1975-9.
[14]
Liang H, Li WH. MicroRNA regulation of human protein protein interaction network. RNA 2007; 13(9): 1402-8.
[15]
Wang C, Jiang W, Li W, et al. Topological properties of the drug targets regulated by microRNA in human protein-protein interaction network. J Drug Target 2011; 19(5): 354-64.
[16]
Zhang Y, Guo X, Xiong L, et al. Comprehensive analysis of microRNA-regulated protein interaction network reveals the tumor suppressive role of microRNA-149 in human hepatocellular carcinoma via targeting AKT-mTOR pathway. Mol Cancer 2014; 13: 253.
[17]
Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochemical and Biophysical Research Communications 2011; 405(2): 153-6.
[18]
Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E. Epigenetic Regulation of HIV-1 Latency by Cytosine Methylation. Plos Pathogens 2009; 5(6): e1000495.
[19]
Weber M, Hellmann I, Stadler MB, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 2007; 39(4): 457-66.
[20]
Valinluck V, Tsai HH, Rogstad DK, et al. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Research 2004; 32(14): 4100-8.
[21]
Nakayama-Hosoya K, Ishida T, Youngblood B, et al. Epigenetic repression of interleukin 2 expression in senescent CD4+ T cells during chronic HIV type 1 infection. J Infect Dis 2015; 211(1): 28-39.
[22]
Gibney ER, Nolan CM. Epigenetics and gene expression. Heredity (Edinb) 2010; 105(1): 4-13.
[23]
Warren K, Warrilow D, Meredith L, Harrich D. Reverse Transcriptase and Cellular Factors: Regulators of HIV-1 Reverse Transcription. Viruses 2009; 1(3): 873-94.
[24]
Bourbigot S, Beltz H, Denis J, et al. The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel dimeric structure in solution via its leucine-zipper-like domain. Biochem J 2005; 387(Pt 2): 333-41.
[25]
Zhao RY, Li G, Bukrinsky MI. Vpr-host interactions during HIV-1 viral life cycle. J Neuroimmune Pharmacol 2011; 6(2): 216-29.
[26]
Sherer NM, Lehmann MJ, Jimenez-Soto LF, et al. Visualization of retroviral replication in living cells reveals budding into multivesicular bodies. Traffic 2003; 4(11): 785-801.
[27]
Wang Q, Mora-Jensen H, Weniger MA, et al. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci USA 2009; 106(7): 2200-5.
[28]
Clarke HJ, Chambers JE, Liniker E, Marciniak SJ. Endoplasmic reticulum stress in malignancy. Cancer Cell 2014; 25(5): 563-73.
[29]
Puoti M, Bruno R, Soriano V, et al. Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome. AIDS 2004; 18(17): 2285-93.
[30]
Perez CL, Milush JM, Buggert M, et al. Targeting of Conserved Gag-Epitopes in Early HIV Infection Is Associated with Lower Plasma Viral Load and Slower CD4(+) T Cell Depletion. Aids Research and Human 2013; 29(3): 602-12.
[31]
Engeland CE, Brown NP, Borner K, et al. Proteome analysis of the HIV-1 Gag interactome. Virology 2014; 460-461: 194-206.
[32]
Lewis B, Whitney S, Hudacik L, et al. Nedd4-mediated increase in HIV-1 Gag and Env proteins and immunity following DNA-vaccination of BALB/c mice. PLoS One 2014; 9(3): e91267.
[33]
Liu J, Wan LX, Liu PD, et al. SCF beta-TRCP-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway. Oncotarget 2014; 5(4): 1026-36.
[34]
Cao Z, Kyprianou N. Mechanisms navigating the TGF-beta pathway in prostate cancer. Asian J Urol 2015; 2(1): 11-8.
[35]
Yang Z, Zhuan B, Yan Y, Jiang S, Wang T. Identification of gene markers in the development of smoking-induced lung cancer. Gene 2016; 576(1 Pt 3): 451-7.
[36]
Weiss ER, Popova E, Yamanaka H, et al. Rescue of HIV-1 release by targeting widely divergent NEDD4-type ubiquitin ligases and isolated catalytic HECT domains to Gag. PLoS Pathog 2010; 6(9): e1001107.
[37]
Houzet L, Klase Z, Yeung ML, et al. The extent of sequence complementarity correlates with the potency of cellular miRNA-mediated restriction of HIV-1. Nucleic Acids Research 2012; 40(22): 11684-96.
[38]
He GC, Margolis DM. Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. Molecular and Cellular Biology 2002; 22(9): 2965-73.
[39]
Spadoni JL, Rucart P, Le Clerc S, et al. Identification of Genes Whose Expression Profile is Associated with Non-Progression towards AIDS Using eQTLs. Plos One 2015; 10(9): e0136989.
[40]
Peterlin BM, Trono D. Hide, shield and strike back: How HIV-infected cells avoid immune eradication. Nature Reviews Immunology 2003; 3(2): 97-107.
[41]
Xie GQ, Yu ZS, Jia DY, Jiao RJ, Deng WM E. E(y)1/TAF9 mediates the transcriptional output of Notch signaling in Drosophila. J Cell Sci 2014; 127(17): 3830-9.
[42]
Mbita Z, Hull R, Dlamini Z. Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets. Viruses-Basel 2014; 6(8): 3181-227.
[43]
Hayes AM, Qian SM, Yu LB, Boris-Lawrie K. Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. Retrovirology 2011; 8: 36.
[44]
Pedersen IM, Cheng G, Wieland S, et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007; 449(7164): 919-U13.
[45]
Santhakumar D, Forster T, Laqtom NN, et al. Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs. Proc Natl Acad Sci USA 2010; 107(31): 13830-5.
[46]
Sanghvi VR, Steel LF. RNA silencing as a cellular defense against HIV-1 infection: progress and issues. Faseb J 2012; 26(10): 3937-45.
[47]
Denkert C, Koch I, von Keyserlingk N, et al. Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2. Modern Pathology 2006; 19(9): 1261-9.
[48]
Kim HC, Choi KC, Choi HK, et al. HDAC3 selectively represses CREB3-mediated transcription and migration of metastatic breast cancer cells. Cell Mol Life Sci 2010; 67(20): 3499-510.
[49]
Li XR, Chu HJ, Lv T, et al. miR-342-3p suppresses proliferation, migration and invasion by targeting FOXM1 in human cervical cancer. FEBS Lett 2014; 588(17): 3298-307.
[50]
Tai MC, Kajino T, Nakatochi M, et al. miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer. Carcinogenesis 2015; 36(12): 1464-73.
[51]
Vo DT, Abdelmohsen K, Martindale JL, et al. The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA Translation and Stability in Glioblastoma Cells. Molecular Cancer Research 2012; 10(1): 143-55.
[52]
Xhemalce B. From histones to RNA: role of methylation in cancer. Brief Funct Genomics 2013; 12(3): 244-53.
[53]
Xu LM, Li LQ, Li J, et al. Overexpression of miR-1260b in Non-small Cell Lung Cancer is Associated with Lymph Node Metastasis. Aging and Disease 2015; 6(6): 478-85.
[54]
Yoon SY, Kim JM, Oh JH, et al. Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags. Int J Oncol 2006; 29(2): 315-27.
[55]
Arion D, Lewis DA. Altered Expression of Regulators of the Cortical Chloride Transporters NKCC1 and KCC2 in Schizophrenia. Archives of General Psychiatry 2011; 68(1): 21-31.
[56]
Sola C, Garcia-Ladona FJ, Mengod G, et al. Increased levels of the Kunitz protease inhibitor-containing beta APP mRNAs in rat brain following neurotoxic damage. Brain Res Mol Brain Res 1993; 17(1-2): 41-52.
[57]
Rodriguez E, Plaud M, Romeu R, Skolasky R, Melendez L. Late HIV infection modulates the expression and activity of Cathepsin B, and its inhibitors in macrophages: implications in neuropathogenesis. Retrovirology 2010; 7: 18-9.
[58]
Chen Z, Manley JL. Robust mRNA transcription in chicken DT40 cells depleted of TAF(II)31 suggests both functional degeneracy and evolutionary divergence. Molecular and Cellular Biology 2000; 20(14): 5064-76.
[59]
Frontini M, Soutoglou E, Argentini M, et al. TAF9b (formerly TAF9L) is a bona fide TAF that has unique and overlapping roles with TAF9. Molecular and Cellular Biology 2005; 25(11): 4638-49.
[60]
Ribet D, Cossart P. Pathogen-mediated posttranslational modifications: A re-emerging field. Cell 2010; 143(5): 694-702.
[61]
Dubrow R, Silverberg MJ, Park LS, Crothers K, Justice AC. HIV infection, aging, and immune function: implications for cancer risk and prevention. Curr Opin Oncol 2012; 24(5): 506-16.
[62]
Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. Aids 2006; 20(12): 1645-54.
[63]
Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-Infected persons compared with the general population in the United States, 1992-2003. Annals of Internal Medicine 2008; 148(10): 728-36.
[64]
Formenti SC, Chak L, Gill P, Buess EM, Hill CK. Increased Radiosensitivity of Normal Tissue Fibroblasts in Patients with Acquired-Immunodeficiency-Syndrome (Aids) and with Kaposis-Sarcoma. Int J Radiat Biol 1995; 68(4): 411-2.
[65]
Ghanam RH, Samal AB, Fernandez TF, Saad JS. Role of the HIV-1 matrix protein in Gag intracellular trafficking and targeting to the plasma membrane for virus assembly. Frontiers in Microbiology 2012; 3: 55.
[66]
Warrilow D, Tachedjian G, Harrich D. Maturation of the HIV reverse transcription complex: putting the jigsaw together. Reviews in Medical Virology 2009; 19(6): 324-37.
[67]
Giroud C, Chazal N, Gay B, et al. HIV-1-associated PKA acts as a cofactor for genome reverse transcription. Retrovirology 2013; 10.
[68]
Leng J, Ho HP, Buzon MJ, et al. A Cell-Intrinsic Inhibitor of HIV-1 Reverse Transcription in CD4(+) T Cells from Elite Controllers. Cell Host & Microbe 2014; 15(6): 717-28.
[69]
Liang C, Hu J, Russell RS, Kameoka M, Wainberg MA. Spliced human immunodeficiency virus type 1 RNA is reverse transcribed into cDNA within infected cells. Aids Research and Human 2004; 20(2): 203-11.
[70]
Pak V, Eifler TT, Jager S, et al. CDK11 in TREX/THOC Regulates HIV mRNA 3′ End Processing. Cell Host Microbe 2015; 18(5): 560-70.
[71]
Berro R, Pedati C, Kehn-Hall K, et al. CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. J Virol 2008; 82(14): 7155-66.
[72]
Aandahl EM, Aukrust P, Skalhegg BS, et al. Protein kinase A type I antagonist restores immune responses of T cells from HIV-infected patients. FASEB J 1998; 12(10): 855-62.
[73]
Ellis J, Hotta A, Rastegar M. Retrovirus silencing by an epigenetic TRIM. Cell 2007; 131(1): 13-4.
[74]
Vang T, Liu WH, Delacroix L, et al. LYP inhibits T-cell activation when dissociated from CSK. Nature Chemical Biology 2012; 8(5): 437-46.
[75]
Pareek TK, Lam E, Zheng XJ, et al. Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis. J Exp Med 2010; 207(11): 2507-19.
[76]
Iordache L, Launay O, Bouchaud O, et al. Autoimmune diseases in HIV-infected patients: 52 cases and literature review. Autoimmun Rev 2014; 13(8): 850-7.
[77]
Gupta P, Liu B, Wu JQ, et al. Genome-wide mRNA and miRNA analysis of peripheral blood mononuclear cells (PBMC) reveals different miRNAs regulating HIV/HCV co-infection. Virology 2014; 450-451: 336-49.
[78]
Wu J, Shen L, Chen J, Xu H, Mao L. The role of microRNAs in enteroviral infections. Braz J Infect Dis 2015; 19(5): 510-6.
[79]
Xu X, Bieda M, Jin VX, et al. A comprehensive ChIP-chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members. Genome Res 2007; 17(11): 1550-61.
[80]
Choi S, Kim HR, Leng L, et al. Role of Macrophage Migration Inhibitory Factor in the Regulatory T Cell Response of Tumor-Bearing Mice. J Immunol 2012; 189(8): 3905-13.
[81]
Ammar A, Sahraoui Y, Tsapis A, et al. Human Immunodeficiency Virus-Infected Adherent Cell-Derived Inhibitory Factor (P-29) Inhibits Normal T-Cell Proliferation through Decreased Expression of High-Affinity Interleukin-2 Receptors and Production of Interleukin-2. J Clin Investigat 1992; 90(1): 8-14.
[82]
Rowbotham SP, Barki L, Neves-Costa A, et al. Maintenance of Silent Chromatin through Replication Requires SWI/SNF-like Chromatin Remodeler SMARCAD1. Molecular Cell 2011; 42(3): 285-96.
[83]
Fatima M, Prajapati B, Saleem K, et al. Novel Insights into Role of miR-320a-VDAC1 Axis in Astrocyte-mediated Neuronal Damage in NeuroAIDS. Glia 2017; 65(2): 250-63.
[84]
Muthumani K, Shedlock DJ, Choo DK, et al. HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in APCs leads to programmed death-1 ligand upregulation and suppression of HIV-specific CD8 T cells. J Immunol 2011; 187(6): 2932-43.
[85]
Myers AP. New strategies in endometrial cancer: targeting the PI3K/mTOR pathway--the devil is in the details. Clin Cancer Res 2013; 19(19): 5264-74.
[86]
Fowler L, Conceicao V, Perera S, et al. First Evidence for the Disease-Stage, Cell-Type, and Virus Specificity of microRNAs during Human Immunodeficiency Virus Type-1 Infection. Medical Sciences 2016; 4(2): E10.
[87]
Christeff N, Gharakhanian S, Thobie N, Rozenbaum W, Nunez EA. Evidence for changes in adrenal and testicular steroids during HIV infection. J Acquir Immune Defic Syndr 1992; 5(8): 841-6.
[88]
Christeff N, Gherbi N, Mammes O, et al. Serum cortisol and DHEA concentrations during HIV infection. Psychoneuroendocrinology 1997; 22(Suppl. 1): S11-8.
[89]
Christeff N, Melchior JC, de Truchis P, et al. Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. Aids 1999; 13(16): 2251-60.
[90]
Christeff N, Melchior JC, Mammes O, et al. Correlation between increased cortisol: DHEA ratio and malnutrition in HIV-positive men. Nutrition 1999; 15(7-8): 534-9.
[91]
Towers G, Harris J, Lang G, Collins MKL, Latchman DS. Retinoic Acid Inhibits Both the Basal Activity and Phorbol Ester-Mediated Activation of the Hiv Long Terminal Repeat Promoter. Aids 1995; 9(2): 129-36.
[92]
Espeseth AS, Fishel R, Hazuda D, et al. siRNA screening of a targeted library of DNA repair factors in HIV infection reveals a role for base excision repair in HIV integration. PLoS One 2011; 6(3): e17612.
[93]
Bushman FD, Malani N, Fernandes J, et al. Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog 2009; 5(5): e1000437.
[94]
Shearer RF, Iconomou M, Watts CK, Saunders DN. Functional Roles of the E3 Ubiquitin Ligase UBR5 in Cancer. Mol Cancer Res 2015; 13(12): 1523-32.
[95]
Drahovsky D, Lacko I, Wacker A. Enzymatic DNA methylation during repair synthesis in non-proliferating human peripheral lymphocytes. Biochim Biophys Acta 1976; 447(2): 139-43.
[96]
Esteller M, Gaidano G, Goodman SN, et al. Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. J Natl Cancer Inst 2002; 94(1): 26-32.
[97]
Baxter J, Sauer S, Peters A, et al. Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. Embo J 2004; 23(22): 4462-72.
[98]
Zhang Y, Zhao M, Sawalha AH, Richardson B, Lu Q. Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus. J Autoimmun 2013; 41: 92-9.
[99]
Emerson V, Holtkotte D, Pfeiffer T, et al. Identification of the Cellular Prohibitin 1/Prohibitin 2 Heterodimer as an Interaction Partner of the C-Terminal Cytoplasmic Domain of the HIV-1 Glycoprotein. J Virol 2010; 84(3): 1355-65.
[100]
Kumar A, Zloza A, Moon RT, et al. Active beta-catenin signaling is an inhibitory pathway for human immunodeficiency virus replication in peripheral blood mononuclear cells. J Virol 2008; 82(6): 2813-20.
[101]
Rajalingam K, Wunder C, Brinkmann V, et al. Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. Nature Cell Biology 2005; 7(8): 837-43.
[102]
Benetti L, Calistri A, Ulivieri C, et al. Inhibition of ShcA isoforms p46/p52Shc enhances HIV-1 replication in CD4+ T-lymphocytes. J Cell Physiol 2004; 199(1): 40-6.
[103]
Catrina SB, Lewitt M, Massambu C, et al. Insulin-like growth factor-I receptor activity is essential for Kaposi’s sarcoma growth and survival. British J Cancer 2005; 92(8): 1467-74.
[104]
Woldt E, Matz RL, Terrand J, et al. Differential signaling by adaptor molecules LRP1 and ShcA regulates adipogenesis by the insulin-like growth factor-1 receptor. J Biol Chem 2011; 286(19): 16775-82.
[105]
Crum NF, Spencer CR, Amling CL. Prostate carcinoma among men with human immunodeficiency virus infection. Cancer 2004; 101(2): 294-9.
[106]
Schlaberg R, Fisher JG, Flamm MJ, et al. Chronic myeloid leukemia and HIV-infection. Leuk Lymphoma 2008; 49(6): 1155-60.
[107]
Miller AM, Lundberg K, Ozenci V, et al. CD4(+)CD25(high) T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol 2006; 177(10): 7398-405.
[108]
Hoxie JA, Alpers JD, Rackowski JL, et al. Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. Science 1986; 234(4780): 1123-7.
[109]
Birge RB, Kalodimos C, Inagaki F, Tanaka S. Crk and CrkL adaptor proteins: networks for physiological and pathological signaling. Cell Commun Signal 2009; 7: 13.
[110]
Minegishi M, Tachibana K, Sato T, et al. Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes. J Exp Med 1996; 184(4): 1365-75.
[111]
Guo M, Shapiro R, Morris GM, Yang XL, Schimmel P. Packaging HIV Virion Components through Dynamic Equilibria of a Human tRNA Synthetase. J Phys Chem B 2010; 114(49): 16273-9.
[112]
Mercenne G, Bernacchi S, Richer D, et al. HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation. Nucleic Acids Res 2010; 38(2): 633-46.
[113]
Park SG, Schimmel P, Kim S. Aminoacyl tRNA synthetases and their connections to disease. Proceedings of the National Academy of Sciences of the United States of America 2008; 105(32): 11043-9.
[114]
Folgueira L, Algeciras A, MacMorran WS, Bren GD, Paya CV. The Ras-Raf pathway is activated in human immunodeficiency virus-infected monocytes and participates in the activation of NF-kappa B. J Virol 1996; 70(4): 2332-8.
[115]
Lyman MG, Randall JA, Calton CM, Banfield BW. Localization of ERK/MAP kinase is regulated by the alphaherpesvirus tegument protein Us2. J Virol 2006; 80(14): 7159-68.
[116]
Geng Y, Whoriskey W, Park MY, et al. Rescue of cyclin D1 deficiency by knockin cyclin E. Cell 1999; 97(6): 767-77.
[117]
Lukas J, Herzinger T, Hansen K, et al. Cyclin E-induced S phase without activation of the pRb/E2F pathway. Genes & Development 1997; 11(11): 1479-92.
[118]
Knudsen ES, Wang JY. Targeting the RB-pathway in cancer therapy. Clin Cancer Res 2010; 16(4): 1094-9.
[119]
Liu L, Ruan J. Network-based Pathway Enrichment Analysis. Proceedings IEEE Int Conf Bioinformatics Biomed 2013; 218-21.
[120]
Agarwal N, Iyer D, Oplt T, et al. Mechanism of HIV-Associated Hepatic Steatosis: Role of HIV-1 Accessory Protein Vpr, Pparalpha and Lxralpha. Endocrine Reviews 2014; 35(3)
[121]
Sterling RK, Smith PG, Brunt EM. Hepatic Steatosis in Human Immunodeficiency Virus A Prospective Study in Patients Without Viral Hepatitis, Diabetes, or Alcohol Abuse. J Clin Gastroenterol 2013; 47(2): 182-7.
[122]
Garron ML, Arthos J, Guichou JF, et al. Structural basis for the interaction between focal adhesion kinase and CD4. J Mol Biol 2008; 375(5): 1320-8.
[123]
Gekonge B, Raymond AD, Yin X, et al. Retinoblastoma protein induction by HIV viremia or CCR5 in monocytes exposed to HIV-1 mediates protection from activation-induced apoptosis: ex vivo and in vitro study. J Leukoc Biol 2012; 92(2): 397-405.
[124]
Bosque A, Planelles V. Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells. Blood 2009; 113(1): 58-65.
[125]
Afonso PV, Zamborlini A, Saib A, Mahieux R. Centrosome and retroviruses: the dangerous liaisons. Retrovirology 2007; 4: 27.
[126]
Herasimtschuk AA, Hansen BR, Langkilde A, et al. Low-dose growth hormone for 40 weeks induces HIV-1-specific T cell responses in patients on effective combination anti-retroviral therapy. Clin Exp Immunol 2013; 173(3): 444-53.
[127]
Quinn J, Astemborski J, Mehta SH, et al. HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline. Pathog Immun 2017; 2(1): 50-9.
[128]
de la Vega M, Marin M, Kondo N, et al. Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion. Retrovirology 2011; 8.
[129]
Swingler S, Zhou J, Swingler C, et al. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe 2008; 4(1): 63-76.
[130]
Muller F, Froland SS, Aukrust P, Fagerhol MK. Elevated Serum Calprotectin Levels in Hiv-Infected Patients - the Calprotectin Response during Zdv Treatment Is Associated with Clinical Events. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 1994; 7(9): 931-9.
[131]
Hung CH, Thomas L, Ruby CE, et al. HIV-1 Nef assembles a Src family kinase-ZAP-70/Syk-PI3K cascade to downregulate cell-surface MHC-I. Cell Host Microbe 2007; 1(2): 121-33.
[132]
Chatr-aryamontri A, Breitkreutz BJ, Oughtred R, et al. The BioGRID interaction database: 2015 update. Nucleic Acids Research 2015; 43(D1): D470-8.
[133]
Fu W, Sanders-Beer BE, Katz KS, et al. Human immunodeficiency virus type 1, human protein interaction database at NCBI. Nucleic Acids Res 2009; 37: D417-22.
[134]
Hsu PWC, Lin LZ, Hsu SD, Hsu JBK, Huang HD. ViTa: prediction of host microRNAs targets on viruses. Nucleic Acids Research 2007; 35: D381-5.
[135]
Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 2014; 42(Database issue): D68-73.
[136]
Lamb J, Crawford ED, Peck D, et al. The connectivity map: Using gene-expression signatures to connect small molecules, genes, and disease. Science 2006; 313(5795): 1929-35.
[137]
Matsunaga A, Hishima T, Tanaka N, et al. DNA methylation profiling can classify HIV-associated lymphomas. Aids 2014; 28(4): 503-10.
[138]
Brass AL, Dykxhoorn DM, Benita Y, et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science 2008; 319(5865): 921-6.
[139]
Konig R, Zhou YY, Elleder D, et al. Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 2008; 135(1): 49-60.
[140]
Zhou HL, Xu M, Huang Q, et al. Genome-Scale RNAi Screen for Host Factors Required for HIV Replication. Cell Host & Microbe 2008; 4(5): 495-504.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 1
Year: 2018
Page: [77 - 95]
Pages: 19
DOI: 10.2174/1570162X16666180219155324

Article Metrics

PDF: 43
HTML: 14
EPUB: 1