Relationship between TLR4 signalling alterations and effective human cytomegalovirus infection

Germini, D.; Arcangeletti, M. C.

doi:10.7124/bc.0008AE

Biopolym. Cell. 2014; 30(5):329-334.

http://dx.doi.org/10.7124/bc.0008AE

Reviews

Relationship between TLR4 signalling alterations and effective human cytomegalovirus infection

1, 2Germini D., 2Arcangeletti M. C.

CNRS UMR 8126, Universit Paris-Sud 11, Institut Gustave Roussy
114, rue Edouard Vaillant, Villejuif, France, 94805
Unit of Microbiology and Virology; Department of Clinical and Experimental Medicine;
University of Parma
via Antonio Gramsci 14, Parma, Italy, 43126

Abstract

Toll-like receptors (TLR), the main class of immune-sensor molecules triggering the innate immunity pathways, are known to be involved in the infection of different RNA and DNA viruses, including herpesviruses. Human cytomegalovirus (HCMV) is a widespread human beta-herpesvirus that infects 80–90 % of the world’s population and it can cause severe and even fatal diseases in immunocompromised patients and it is also responsible for birth defects as a consequence of congenital infection. Aim of this review is to discuss the existing data regarding the role of TLRs in HCMV concentrating mainly on TLR4. A better understanding in this relationship could be exploited for the development of efficient early diagnosis methodologies and anti viral therapies.

Keywords: human cytomegalovirus, Toll-like receptors, innate immune response

Full text: (PDF, in English)

References

[1] Mocarski ES, Courcelle CT. Cytomegalovirus and their replication. Fields Virology. Philadelphia, 2001; 2629–73.

[2] Alford CA, Britt WJ. Cytomegalovirus. Fields Virology. Philadelphia, 1996; 2493–534.

[3] Bosch W, Heckman MG, Diehl NN, Shalev JA, Pungpapong S, Hellinger WC. Association of cytomegalovirus infection and disease with death and graft loss after liver transplant in high-risk recipients. Am J Transplant. 2011;11(10):2181-9.

[4] Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, Nabors LB, Cobbs CG, Britt WJ. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62(12):3347-50.

[5] Pass RF. Cytomegalovirus. Fields Virology. Philadelphia, 2001; 2575–705.

[6] Ramsay ME, Miller E, Peckham CS. Outcome of confirmed symptomatic congenital cytomegalovirus infection. Arch Dis Child. 1991;66(9):1068-9.

[7] Razonable RR, Paya CV. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and Epstein-Barr virus infections. Herpes. 2003;10(3):60-5.

[8] Lunardi C, Bason C, Corrocher R, Puccetti A. Induction of endothelial cell damage by hCMV molecular mimicry. Trends Immunol. 2005;26(1):19-24.

[9] S?derberg-Naucl?r C, Streblow DN, Fish KN, Allan-Yorke J, Smith PP, Nelson JA. Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent. J Virol. 2001;75(16):7543-54.

[10] Varani S, Landini MP. Cytomegalovirus-induced immunopathology and its clinical consequences. Herpesviridae. 2011;2(1):6.

[11] Arrode G, Davrinche C. Dendritic cells and HCMV cross-presentation. Curr Top Microbiol Immunol. 2003;276:277-94.

[12] R?lle A, Olweus J. Dendritic cells in cytomegalovirus infection: viral evasion and host countermeasures. APMIS. 2009;117(5-6):413-26.

[13] Slobedman B, Stern JL, Cunningham AL, Abendroth A, Abate DA, Mocarski ES. Impact of human cytomegalovirus latent infection on myeloid progenitor cell gene expression. J Virol. 2004;78(8):4054-62.

[14] Ioudinkova E, Arcangeletti MC, Rynditch A, De Conto F, Motta F, Covan S, Pinardi F, Razin SV, Chezzi C. Control of human cytomegalovirus gene expression by differential histone modifications during lytic and latent infection of a monocytic cell line. Gene. 2006;384:120-8.

[15] Smith MS, Bentz GL, Alexander JS, Yurochko AD. Human cytomegalovirus induces monocyte differentiation and migration as a strategy for dissemination and persistence. J Virol. 2004;78(9):4444-53.

[16] Billstrom Schroeder M, Christensen R, Worthen GS. Human cytomegalovirus protects endothelial cells from apoptosis induced by growth factor withdrawal. J Clin Virol. 2002;25 Suppl 2:S149-57.

[17] Castillo JP, Kowalik TF. HCMV infection: modulating the cell cycle and cell death. Int Rev Immunol. 2004;23(1-2):113-39.

[18] Compton T, Kurt-Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, Finberg RW. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol. 2003;77(8):4588-96.

[19] Hertel L, Mocarski ES. Global analysis of host cell gene expression late during cytomegalovirus infection reveals extensive dysregulation of cell cycle gene expression and induction of Pseudomitosis independent of US28 function. J Virol. 2004;78(21):11988-2011.

[20] Salsman J, Jagannathan M, Paladino P, Chan PK, Dellaire G, Raught B, Frappier L. Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response. J Virol. 2012;86(2):806-20.

[21] Wolf J, Weinberger B, Grubeck-Loebenstein B. The immunoregulatory effects of CMV-infection in human fibroblasts and the impact on cellular senescence. Immun Ageing. 2012;9:1.

[22] Boehme KW, Guerrero M, Compton T. Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J Immunol. 2006;177(10):7094-102.

[23] Cai MS, Li ML, Zheng CF. Herpesviral infection and Toll-like receptor 2. Protein Cell. 2012;3(8):590-601.

[24] Ducloux D, Deschamps M, Yannaraki M, Ferrand C, Bamoulid J, Saas P, Kazory A, Chalopin JM, Tiberghien P. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation. Kidney Int. 2005;67(6):2454-61.

[25] Gaur P, Munjhal A, Lal SK. Influenza virus and cell signaling pathways. Med Sci Monit. 2011;17(6):RA148-54.

[26] Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW. Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A. 2004;101(5):1315-20.

[27] L?fgren J, Marttila R, Renko M, R?met M, Hallman M. Toll-like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics. Pediatr Pulmonol. 2010;45(7):687-92.

[28] Xagorari A, Chlichlia K. Toll-like receptors and viruses: induction of innate antiviral immune responses. Open Microbiol J. 2008;2:49-59.

[29] Malmgaard L, Melchjorsen J, Bowie AG, Mogensen SC, Paludan SR. Viral activation of macrophages through TLR-dependent and -independent pathways. J Immunol. 2004;173(11):6890-8.

[30] Remer KA, Brcic M, Sauter KS, Jungi TW. Human monocytoid cells as a model to study Toll-like receptor-mediated activation. J Immunol Methods. 2006;313(1-2):1-10.

[31] van der Kleij D, van den Biggelaar AH, Kruize YC, Retra K, Fillie Y, Schmitz M, Kremsner PG, Tielens AG, Yazdanbakhsh M. Responses to Toll-like receptor ligands in children living in areas where schistosome infections are endemic. J Infect Dis. 2004;189(6):1044-51.

[32] Juckem LK, Boehme KW, Feire AL, Compton T. Differential initiation of innate immune responses induced by human cytomegalovirus entry into fibroblast cells. J Immunol. 2008;180(7):4965-77.

[33] Chan G, Guilbert LJ. Ultraviolet-inactivated human cytomegalovirus induces placental syncytiotrophoblast apoptosis in a Toll-like receptor-2 and tumour necrosis factor-alpha dependent manner. J Pathol. 2006;210(1):111-20.

[34] Rossini G, Cerboni C, Santoni A, Landini MP, Landolfo S, Gatti D, Gribaudo G, Varani S. Interplay between human cytomegalovirus and intrinsic/innate host responses: a complex bidirectional relationship. Mediators Inflamm. 2012;2012:607276.

[35] Bieback K, Lien E, Klagge IM, Avota E, Schneider-Schaulies J, Duprex WP, Wagner H, Kirschning CJ, Ter Meulen V, Schneider-Schaulies S. Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling. J Virol. 2002;76(17):8729-36.

[36] Desombere I, Hauser P, Rossau R, Paradijs J, Leroux-Roels G. Nonresponders to hepatitis B vaccine can present envelope particles to T lymphocytes. J Immunol. 1995;154(2):520-9.

[37] H?hler T, Reuss E, Evers N, Dietrich E, Rittner C, Freitag CM, Vollmar J, Schneider PM, Fimmers R. Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins. Lancet. 2002;360(9338):991-5.

[38] Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, Walsh EE, Freeman MW, Golenbock DT, Anderson LJ, Finberg RW. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398-401.

[39] Pankratz VS, Vierkant RA, O'Byrne MM, Ovsyannikova IG, Poland GA. Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment. BMC Immunol. 2010;11:48.

[40] Poland GA. Variability in immune response to pathogens: using measles vaccine to probe immunogenetic determinants of response. Am J Hum Genet. 1998;62(2):215-20.

[41] Wang C, Tang J, Song W, Lobashevsky E, Wilson CM, Kaslow RA. HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination. Hepatology. 2004;39(4):978-88.

[42] Netea MG, Wijmenga C, O'Neill LA. Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol. 2012;13(6):535-42.

[43] Texereau J, Chiche JD, Taylor W, Choukroun G, Comba B, Mira JP. The importance of Toll-like receptor 2 polymorphisms in severe infections. Clin Infect Dis. 2005;41 Suppl 7:S408-15.

[44] Wang JJ, Xia X, Tang SD, Wang J, Deng XZ, Zhang Y, Yue M. Meta-analysis on the associations of TLR2 gene polymorphisms with pulmonary tuberculosis susceptibility among Asian populations. PLoS One. 2013;8(10):e75090.

[45] Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T, Herz U, Heeg K, Neumaier M, Renz H. The toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol. 2004;113(3):565-7.

[46] Kormann MS, Ferstl R, Depner M, Klopp N, Spiller S, Illig T, Vogelberg C, von Mutius E, Kirschning CJ, Kabesch M. Rare TLR2 mutations reduce TLR2 receptor function and can increase atopy risk. Allergy. 2009;64(4):636-42.

[47] Lazarus R, Klimecki WT, Raby BA, Vercelli D, Palmer LJ, Kwiatkowski DJ, Silverman EK, Martinez F, Weiss ST. Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U.S. ethnic groups and exploratory case-control disease association studies. Genomics. 2003;81(1):85-91.

[48] Nahum A, Dadi H, Bates A, Roifman CM. The biological significance of TLR3 variant, L412F, in conferring susceptibility to cutaneous candidiasis, CMV and autoimmunity. Autoimmun Rev. 2012;11(5):341-7.

[49] Kang SH, Abdel-Massih RC, Brown RA, Dierkhising RA, Kremers WK, Razonable RR. Homozygosity for the toll-like receptor 2 R753Q single-nucleotide polymorphism is a risk factor for cytomegalovirus disease after liver transplantation. J Infect Dis. 2012;205(4):639-46.

[50] Kijpittayarit S, Eid AJ, Brown RA, Paya CV, Razonable RR. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin Infect Dis. 2007;44(10):1315-20.

[51] Brown RA, Gralewski JH, Razonable RR. The R753Q polymorphism abrogates toll-like receptor 2 signaling in response to human cytomegalovirus. Clin Infect Dis. 2009;49(9):e96-9.

[52] Jab?o?ska A, Paradowska E, Studzi?ska M, Suski P, Nowakowska D, Wi?niewska-Ligier M, Wo?niakowska-G?sicka T, Wilczy?ski J, Le?nikowski ZJ. Relationship between toll-like receptor 2 Arg677Trp and Arg753Gln and toll-like receptor 4 Asp299Gly polymorphisms and cytomegalovirus infection. Int J Infect Dis. 2014;25:11-5.

[53] Arcangeletti MC, Germini D, Rodighiero I, Mirandola P, De Conto F, Medici MC, Gatti R, Chezzi C, Calderaro A. Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages. Virology. 2013;440(1):19-30.

[54] Lor? K, Betts MR, Brenchley JM, Kuruppu J, Khojasteh S, Perfetto S, Roederer M, Seder RA, Koup RA. Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J Immunol. 2003;171(8):4320-8.

[55] Isomura H, Stinski MF. The human cytomegalovirus major immediate-early enhancer determines the efficiency of immediate-early gene transcription and viral replication in permissive cells at low multiplicity of infection. J Virol. 2003;77(6):3602-14.

[56] Fox-Canale AM, Hope TJ, Martinson J, Lurain JR, Rademaker AW, Bremer JW, Landay A, Spear GT, Lurain NS. Human cytomegalovirus and human immunodeficiency virus type-1 co-infection in human cervical tissue. Virology. 2007;369(1):55-68.

[57] Harwani SC, Lurain NS, Zariffard MR, Spear GT. Differential inhibition of human cytomegalovirus (HCMV) by toll-like receptor ligands mediated by interferon-beta in human foreskin fibroblasts and cervical tissue. Virol J. 2007;4:133.

[58] Fitzgerald KA, Chen ZJ. Sorting out Toll signals. Cell. 2006;125(5):834-6.

[59] Xie XH, Law HK, Wang LJ, Li X, Yang XQ, Liu EM. Lipopolysaccharide induces IL-6 production in respiratory syncytial virus-infected airway epithelial cells through the toll-like receptor 4 signaling pathway. Pediatr Res. 2009;65(2):156-62.

[60] Watts C. Location, location, location: identifying the neighborhoods of LPS signaling. Nat Immunol. 2008;9(4):343-5.

[61] Akashi S, Saitoh S, Wakabayashi Y, Kikuchi T, Takamura N, Nagai Y, Kusumoto Y, Fukase K, Kusumoto S, Adachi Y, Kosugi A, Miyake K. Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: higher affinity than that with MD-2 or CD14. J Exp Med. 2003;198(7):1035-42.

[62] Kennedy MN, Mullen GE, Leifer CA, Lee C, Mazzoni A, Dileepan KN, Segal DM. A complex of soluble MD-2 and lipopolysaccharide serves as an activating ligand for Toll-like receptor 4. J Biol Chem. 2004;279(33):34698-704.

[63] Sacre SM, Lundberg AM, Andreakos E, Taylor C, Feldmann M, Foxwell BM. Selective use of TRAM in lipopolysaccharide (LPS) and lipoteichoic acid (LTA) induced NF-kappaB activation and cytokine production in primary human cells: TRAM is an adaptor for LPS and LTA signaling. J Immunol. 2007;178(4):2148-54.

[64] Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K. Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Biochem Biophys Res Commun. 2008;368(1):94-9.

[65] Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K, Akira S. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol. 2003;4(11):1144-50.

[66] Yew KH, Carpenter C, Duncan RS, Harrison CJ. Human cytomegalovirus induces TLR4 signaling components in monocytes altering TIRAP, TRAM and downstream interferon-beta and TNF-alpha expression. PLoS One. 2012;7(9):e44500.

[67] Humar A, St Louis P, Mazzulli T, McGeer A, Lipton J, Messner H, MacDonald KS. Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients. J Infect Dis. 1999;179(2):484-8.

[68] Hasan UA, Trinchieri G, Vlach J. Toll-like receptor signaling stimulates cell cycle entry and progression in fibroblasts. J Biol Chem. 2005;280(21):20620-7.

[69] Hasan UA, Caux C, Perrot I, Doffin AC, Menetrier-Caux C, Trinchieri G, Tommasino M, Vlach J. Cell proliferation and survival induced by Toll-like receptors is antagonized by type I IFNs. Proc Natl Acad Sci U S A. 2007;104(19):8047-52.

[70] Arcangeletti MC, Rodighiero I, Mirandola P, De Conto F, Covan S, Germini D, Razin S, Dettori G, Chezzi C. Cell-cycle-dependent localization of human cytomegalovirus UL83 phosphoprotein in the nucleolus and modulation of viral gene expression in human embryo fibroblasts in vitro. J Cell Biochem. 2011;112(1):307-17.

[71] Bain M, Sinclair J. The S phase of the cell cycle and its perturbation by human cytomegalovirus. Rev Med Virol. 2007;17(6):423-34.

[72] Fortunato EA, Sanchez V, Yen JY, Spector DH. Infection of cells with human cytomegalovirus during S phase results in a blockade to immediate-early gene expression that can be overcome by inhibition of the proteasome. J Virol. 2002;76(11):5369-79.

[73] Sinclair J, Baillie J, Bryant L, Caswell R. Human cytomegalovirus mediates cell cycle progression through G(1) into early S phase in terminally differentiated cells. J Gen Virol. 2000;81(Pt 6):1553-65.

[74] Song YJ, Stinski MF. Inhibition of cell division by the human cytomegalovirus IE86 protein: role of the p53 pathway or cyclin-dependent kinase 1/cyclin B1. J Virol. 2005;79(4):2597-603.

[75] Wiebusch L, Asmar J, Uecker R, Hagemeier C. Human cytomegalovirus immediate-early protein 2 (IE2)-mediated activation of cyclin E is cell-cycle-independent and forces S-phase entry in IE2-arrested cells. J Gen Virol. 2003;84(Pt 1):51-60.

[76] Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25(2):187-91.

[77] Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, Willeit J, Schwartz DA. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med. 2002;347(3):185-92.

[78] Agnese DM, Calvano JE, Hahm SJ, Coyle SM, Corbett SA, Calvano SE, Lowry SF. Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J Infect Dis. 2002;186(10):1522-5.

[79] Lorenz E, Mira JP, Frees KL, Schwartz DA. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002;162(9):1028-32.

[80] Van der Graaf CA, Netea MG, Morr? SA, Den Heijer M, Verweij PE, Van der Meer JW, Kullberg BJ. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur Cytokine Netw. 2006;17(1):29-34.

[81] Rezazadeh M, Hajilooi M, Rafiei A, Haidari M, Nikoopour E, Kerammat F, Mamani M, Ranjbar M, Hashemi H. TLR4 polymorphism in Iranian patients with brucellosis. J Infect. 2006;53(3):206-10.

[82] Tal G, Mandelberg A, Dalal I, Cesar K, Somekh E, Tal A, Oron A, Itskovich S, Ballin A, Houri S, Beigelman A, Lider O, Rechavi G, Amariglio N. Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J Infect Dis. 2004;189(11):2057-63.

[83] Mockenhaupt FP, Cramer JP, Hamann L, Stegemann MS, Eckert J, Oh NR, Otchwemah RN, Dietz E, Ehrhardt S, Schr?der NW, Bienzle U, Schumann RR. Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci U S A. 2006;103(1):177-82.

[84] Netea MG, Warris A, Van der Meer JW, Fenton MJ, Verver-Janssen TJ, Jacobs LE, Andresen T, Verweij PE, Kullberg BJ. Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis. 2003;188(2):320-6.

[85] Bochud PY, Chien JW, Marr KA, Leisenring WM, Upton A, Janer M, Rodrigues SD, Li S, Hansen JA, Zhao LP, Aderem A, Boeckh M. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med. 2008;359(17):1766-77.