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.
Graphical Abstract
[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.
[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.
[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.
Call for Papers in Thematic Issues
28 April, 2024
Management of HIV: Management of HIV: old challenges and new needs
The aim of this thematic issue is to provide the most recent updates regarding the effective management of HIV infection. Antiretroviral therapy (ART) has significantly decreased HIV-related mortality, leading to an enhancement in the quality of life and life expectancy for people living with HIV (PLWH). Despite the numerous advancements ...read more
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