Skip to main content

Advertisement

SpringerLink
Log in

Kaposi sarcoma-associated herpes virus (KSHV) latent protein LANA modulates cellular genes associated with epithelial-to-mesenchymal transition

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Kaposi’s sarcoma-associated herpes virus (KSHV) is a gammaherpesvirus associated with Kaposi’s sarcoma and various lymphoproliferative diseases. Epithelial-to-mesenchymal transition (EMT) is an important step in the metastasis of cancer cells. Previous studies have shown an important role for EMT markers in B-cell malignancies. In the present study, we investigated the role of the KSHV latent protein LANA in the progression of EMT. Our data suggest that expression of LANA results in an increase in the migration and invasion potential of cancer cells, which is concurrent with modulation of transcriptional regulation and protein expression of several cellular genes associated with EMT. LANA expression results in upregulation of the cellular intermediate filament protein vimentin and transcription factor TCF8/ZEB1 and downregulation of tight junction protein ZO1 and adhesion protein E-cadherin. LANA co-localizes with TCF8/ZEB1, a major contributor in EMT, further suggesting an important role for LANA in epithelial-to-mesenchymal transition of KSHV-infected cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3(6):453–458. https://doi.org/10.1038/nrc1098

    Article  PubMed  CAS  Google Scholar 

  2. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454. https://doi.org/10.1038/nrc822

    Article  PubMed  CAS  Google Scholar 

  3. Gatenby RA (2009) A change of strategy in the war on cancer. Nature 459(7246):508–509. https://doi.org/10.1038/459508a

    Article  PubMed  CAS  Google Scholar 

  4. Patel LR, Camacho DF, Shiozawa Y, Pienta KJ, Taichman RS (2011) Mechanisms of cancer cell metastasis to the bone: a multistep process. Future Oncol 7(11):1285–1297. https://doi.org/10.2217/fon.11.112

    Article  PubMed  CAS  Google Scholar 

  5. Pienta KJ, Loberg R (2005) The “emigration, migration, and immigration” of prostate cancer. Clin Prostate Cancer 4(1):24–30

    Article  PubMed  Google Scholar 

  6. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Investig 119(6):1420–1428. https://doi.org/10.1172/JCI39104

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Goossens S, Vandamme N, Van Vlierberghe P (1868) Berx G (2017) EMT transcription factors in cancer development re-evaluated: beyond EMT and MET. Biochim Biophys Acta 2:584–591

    Google Scholar 

  8. Lee JM, Dedhar S, Kalluri R, Thompson EW (2006) The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172(7):973–981

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939. https://doi.org/10.1016/j.cell.2004.06.006

    Article  PubMed  CAS  Google Scholar 

  10. Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A (2003) The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 116(Pt 3):499–511

    Article  PubMed  CAS  Google Scholar 

  11. Hajra KM, Chen DY, Fearon ER (2002) The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 62(6):1613–1618

    PubMed  CAS  Google Scholar 

  12. Turner FE, Broad S, Khanim FL, Jeanes A, Talma S, Hughes S, Tselepis C, Hotchin NA (2006) Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes. J Biol Chem 281(30):21321–21331

    Article  PubMed  CAS  Google Scholar 

  13. Zhang P, Sun Y, Ma L (2015) ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle 14(4):481–487. https://doi.org/10.1080/15384101.2015.1006048

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Ishida K, Ito S, Wada N, Deguchi H, Hata T, Hosoda M, Nohno T (2007) Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia. Mol Cancer 6:62

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Cadigan KM, Nusse R (1997) Wnt signaling: a common theme in animal development. Genes Dev 11(24):3286–3305

    Article  PubMed  CAS  Google Scholar 

  16. Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT (1999) SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Mol Cell 4(3):343–352

    Article  PubMed  CAS  Google Scholar 

  17. Schmidt CR, Gi YJ, Patel TA, Coffey RJ, Beauchamp RD, Pearson AS (2005) E-cadherin is regulated by the transcriptional repressor SLUG during Ras-mediated transformation of intestinal epithelial cells. Surgery 138(2):306–312

    Article  PubMed  Google Scholar 

  18. Adhikary A, Chakraborty S, Mazumdar M, Ghosh S, Mukherjee S, Manna A, Mohanty S, Nakka KK, Joshi S, De A, Chattopadhyay S, Sa G, Das T (2014) Inhibition of epithelial to mesenchymal transition by E-cadherin up-regulation via repression of slug transcription and inhibition of E-cadherin degradation: dual role of scaffold/matrix attachment region-binding protein 1 (SMAR1) in breast cancer cells. J Biol Chem 289(37):25431–25444. https://doi.org/10.1074/jbc.M113.527267M

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Sakai D, Tanaka Y, Endo Y, Osumi N, Okamoto H, Wakamatsu Y (2005) Regulation of Slug transcription in embryonic ectoderm by beta-catenin-Lef/Tcf and BMP-Smad signaling. Dev Growth Differ 47(7):471–482

    Article  PubMed  CAS  Google Scholar 

  20. Cai LM, Lyu XM, Luo WR, Cui XF, Ye YF, Yuan CC, Peng QX, Wu DH, Liu TF, Wang E, Marincola FM, Yao KT, Fang WY, Cai HB, Li X (2015) EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN. Oncogene 34(17):2156–2166. https://doi.org/10.1038/onc.2014.341

    Article  PubMed  CAS  Google Scholar 

  21. Chung TW, Kim SJ, Choi HJ, Song KH, Jin UH, Yu DY, Seong JK, Kim JG, Kim KJ, Ko JH, Ha KT, Lee YC, Kim CH (2014) Hepatitis B virus X protein specially regulates the sialyl lewis a synthesis among glycosylation events for metastasis. Mol Cancer 13:222. https://doi.org/10.1186/1476-4598-13-222

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Harakeh S, Abou-Khouzam R, Damanhouri GA, Al-Hejin A, Kumosani T, Niedzwiecki A, Rath M, Barbour E, Diab-Assaf M, Azar R (2014) Effects of nutrients on matrix metalloproteinases in human T-lymphotropic virus type 1 positive and negative malignant T-lymphocytes. Int J Oncol 45(5):2159–2166. https://doi.org/10.3892/ijo.2014.2638

    Article  PubMed  CAS  Google Scholar 

  23. Knight LM, Stakaityte G, Wood JJ, Abdul-Sada H, Griffiths DA, Howell GJ, Wheat R, Blair GE, Steven NM, Macdonald A, Blackbourn DJ, Whitehouse A (2015) Merkel cell polyomavirus small T antigen mediates microtubule destabilization to promote cell motility and migration. J Virol 89(1):35–47. https://doi.org/10.1128/JVI.02317-14

    Article  PubMed  CAS  Google Scholar 

  24. Gaur N, Gandhi J, Robertson ES, Verma SC, Kaul R (2015) Epstein-Barr virus latent antigens EBNA3C and EBNA1 modulate epithelial to mesenchymal transition of cancer cells associated with tumor metastasis. Tumour Biol 36(4):3051–3060. https://doi.org/10.1007/s13277-014-2941-6

    Article  PubMed  CAS  Google Scholar 

  25. Moore PS, Chang Y (2003) Kaposi’s sarcoma-associated herpesvirus immunoevasion and tumorigenesis: two sides of the same coin? Annu Rev Microbiol 57:609–639. https://doi.org/10.1146/annurev.micro.57.030502.090824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Ignatovich IA, Dizhe EB, Akif’ev BN, Burov SV, Boiarchuk EA, Perevozchikov AP (2002) Delivery of “suicide” thymidine kinase gene of herpes virus in the complex with cationic peptide into human hepatoma cells in vitro. Tsitologiia 44(5):455–462

    PubMed  CAS  Google Scholar 

  27. Lemma S, Karihtala P, Haapasaari KM, Jantunen E, Soini Y, Bloigu R, Pasanen AK, Turpeenniemi-Hujanen T, Kuittinen O (2013) Biological roles and prognostic values of the epithelial-mesenchymal transition-mediating transcription factors Twist, ZEB1 and Slug in diffuse large B-cell lymphoma. Histopathology 62(2):326–333. https://doi.org/10.1111/his.12000

    Article  PubMed  Google Scholar 

  28. Sanchez-Tillo E, Fanlo L, Siles L, Montes-Moreno S, Moros A, Chiva-Blanch G, Estruch R, Martinez A, Colomer D, Gyorffy B, Roue G, Postigo A (2014) The EMT activator ZEB1 promotes tumor growth and determines differential response to chemotherapy in mantle cell lymphoma. Cell Death Differ 21(2):247–257. https://doi.org/10.1038/cdd.2013.123

    Article  PubMed  CAS  Google Scholar 

  29. Jha HC, Sun Z, Upadhyay SK, El-Naccache DW, Singh RK, Sahu SK, Robertson ES (2016) KSHV-mediated regulation of Par3 and SNAIL contributes to B-Cell proliferation. PLoS Pathog 12(7):e1005801. https://doi.org/10.1371/journal.ppat.1005801

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Gasperini P, Espigol-Frigole G, McCormick PJ, Salvucci O, Maric D, Uldrick TS, Polizzotto MN, Yarchoan R, Tosato G (2012) Kaposi sarcoma herpesvirus promotes endothelial-to-mesenchymal transition through Notch-dependent signaling. Cancer Res 72(5):1157–1169. https://doi.org/10.1158/0008-5472.CAN-11-3067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Cheng F, Pekkonen P, Laurinavicius S, Sugiyama N, Henderson S, Gunther T, Rantanen V, Kaivanto E, Aavikko M, Sarek G, Hautaniemi S, Biberfeld P, Aaltonen L, Grundhoff A, Boshoff C, Alitalo K, Lehti K, Ojala PM (2011) KSHV-initiated notch activation leads to membrane-type-1 matrix metalloproteinase-dependent lymphatic endothelial-to-mesenchymal transition. Cell Host Microbe 10(6):577–590. https://doi.org/10.1016/j.chom.2011.10.011S1931-3128(11)00364-7

    Article  PubMed  CAS  Google Scholar 

  32. Dourmishev LA, Dourmishev AL, Palmeri D, Schwartz RA, Lukac DM (2003) Molecular genetics of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis. Microbiol Mol Biol Rev 67(2):175–212 (table of contents)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Ballestas ME, Chatis PA, Kaye KM (1999) Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284(5414):641–644

    Article  PubMed  CAS  Google Scholar 

  34. Borah S, Verma SC, Robertson ES (2004) ORF73 of herpesvirus saimiri, a viral homolog of Kaposi’s sarcoma-associated herpesvirus, modulates the two cellular tumor suppressor proteins p53 and pRb. J Virol 78(19):10336–10347. https://doi.org/10.1128/JVI.78.19.10336-10347.2004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Friborg J Jr, Kong W, Hottiger MO, Nabel GJ (1999) p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402(6764):889–894. https://doi.org/10.1038/47266

    Article  PubMed  CAS  Google Scholar 

  36. Fujimuro M, Hayward SD (2003) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus manipulates the activity of glycogen synthase kinase-3beta. J Virol 77(14):8019–8030

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Verma SC, Lan K, Choudhuri T, Cotter MA, Robertson ES (2007) An autonomous replicating element within the KSHV genome. Cell Host Microbe 2(2):106–118

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Verma SC, Choudhuri T, Kaul R, Robertson ES (2006) Latency-associated nuclear antigen (LANA) of Kaposi’s sarcoma-associated herpesvirus interacts with origin recognition complexes at the LANA binding sequence within the terminal repeats. J Virol 80(5):2243–2256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Khera L, Paul C, Kaul R (2017) Hepatitis C Virus E1 protein promotes cell migration and invasion by modulating cellular metastasis suppressor Nm23-H1. Virology 506:110–120

    Article  PubMed  CAS  Google Scholar 

  40. Rueden CT, Schindelin J, Hiner MC, DeZonia BE, Walter AE, Arena ET, Eliceiri KW (2017) Image J2: ImageJ for the next generation of scientific image data. BMC Bioinform 18(1):529. https://doi.org/10.1186/s12859-017-1934-z

    Article  Google Scholar 

  41. Huang RY, Guilford P, Thiery JP (2012) Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci 125(Pt 19):4417–4422. https://doi.org/10.1242/jcs.099697

    Article  PubMed  CAS  Google Scholar 

  42. Nishimura G, Manabe I, Tsushima K, Fujiu K, Oishi Y, Imai Y, Maemura K, Miyagishi M, Higashi Y, Kondoh H, Nagai R (2006) DeltaEF1 mediates TGF-beta signaling in vascular smooth muscle cell differentiation. Dev Cell 11(1):93–104

    Article  PubMed  CAS  Google Scholar 

  43. Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA (2007) A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin Cancer Res 13(23):7003–7011

    Article  PubMed  CAS  Google Scholar 

  44. Dittmer DP, Damania B (2016) Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. J Clin Investig 126(9):3165–3175. https://doi.org/10.1172/JCI84418

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kelley-Clarke B, De Leon-Vazquez E, Slain K, Barbera AJ, Kaye KM (2009) Role of Kaposi’s sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence. J Virol 83(9):4326–4337. https://doi.org/10.1128/JVI.02395-08

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC, Luger K, Kaye KM (2006) The nucleosomal surface as a docking station for Kaposi’s sarcoma herpesvirus LANA. Science 311(5762):856–861

    Article  PubMed  CAS  Google Scholar 

  47. Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15(3):178–196. https://doi.org/10.1038/nrm3758

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Whitaker HC, Girling J, Warren AY, Leung H, Mills IG, Neal DE (2008) Alterations in beta-catenin expression and localization in prostate cancer. Prostate 68(11):1196–1205. https://doi.org/10.1002/pros.20780

    Article  PubMed  CAS  Google Scholar 

  49. Schmalhofer O, Brabletz S, Brabletz T (2009) E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev 28(1–2):151–166. https://doi.org/10.1007/s10555-008-9179-y

    Article  PubMed  CAS  Google Scholar 

  50. Wheelock MJ, Johnson KR (2003) Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol 19:207–235. https://doi.org/10.1146/annurev.cellbio.19.011102.111135

    Article  PubMed  CAS  Google Scholar 

  51. Wells A, Chao YL, Grahovac J, Wu Q, Lauffenburger DA (2011) Epithelial and mesenchymal phenotypic switchings modulate cell motility in metastasis. Front Biosci (Landmark Ed) 16:815–837

    Article  CAS  Google Scholar 

  52. Matter K, Balda MS (2007) Epithelial tight junctions, gene expression and nucleo-junctional interplay. J Cell Sci 120(Pt 9):1505–1511

    Article  PubMed  CAS  Google Scholar 

  53. Liu Y, El-Naggar S, Darling DS, Higashi Y, Dean DC (2008) Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development 135(3):579–588. https://doi.org/10.1242/dev.007047

    Article  PubMed  CAS  Google Scholar 

  54. Weber KL, Doucet M, Price JE (2003) Renal cell carcinoma bone metastasis: epidermal growth factor receptor targeting. Clin Orthop Relat Res 415(Suppl):S86–S94. https://doi.org/10.1097/01.blo.0000093050.96273.35

    Article  Google Scholar 

  55. Singh M, Spoelstra NS, Jean A, Howe E, Torkko KC, Clark HR, Darling DS, Shroyer KR, Horwitz KB, Broaddus RR, Richer JK (2008) ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease. Mod Pathol 21(7):912–923. https://doi.org/10.1038/modpathol.2008.82

    Article  PubMed  CAS  Google Scholar 

  56. Karihtala P, Auvinen P, Kauppila S, Haapasaari KM, Jukkola-Vuorinen A, Soini Y (2013) Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype. Breast Cancer Res Treat 138(1):81–90. https://doi.org/10.1007/s10549-013-2442-0

    Article  PubMed  CAS  Google Scholar 

  57. Ohira T, Gemmill RM, Ferguson K, Kusy S, Roche J, Brambilla E, Zeng C, Baron A, Bemis L, Erickson P, Wilder E, Rustgi A, Kitajewski J, Gabrielson E, Bremnes R, Franklin W, Drabkin HA (2003) WNT7a induces E-cadherin in lung cancer cells. Proc Natl Acad Sci USA 100(18):10429–10434. https://doi.org/10.1073/pnas.1734137100

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  58. Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L, Helfrich B, Dziadziuszko R, Chan DC, Sugita M, Chan Z, Baron A, Franklin W, Drabkin HA, Girard L, Gazdar AF, Minna JD, Bunn PA Jr (2006) Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 66(2):944–950

    Article  PubMed  CAS  Google Scholar 

  59. Kaul R, Murakami M, Choudhuri T, Robertson ES (2007) Epstein-Barr virus latent nuclear antigens can induce metastasis in a nude mouse model. J Virol 81(19):10352–10361

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Silverberg MJ, Lau B, Achenbach CJ, Jing Y, Althoff KN, D’Souza G, Engels EA, Hessol NA, Brooks JT, Burchell AN, Gill MJ, Goedert JJ, Hogg R, Horberg MA, Kirk GD, Kitahata MM, Korthuis PT, Mathews WC, Mayor A, Modur SP, Napravnik S, Novak RM, Patel P, Rachlis AR, Sterling TR, Willig JH, Justice AC, Moore RD, Dubrow R (2015) Cumulative incidence of cancer among persons with HIV in North America: a cohort study. Ann Intern Med 163(7):507–518. https://doi.org/10.7326/M14-2768

    Article  PubMed  PubMed Central  Google Scholar 

  61. Robbins HA, Pfeiffer RM, Shiels MS, Li J, Hall HI, Engels EA (2015) Excess cancers among HIV-infected people in the United States. J Natl Cancer Inst. https://doi.org/10.1093/jnci/dju503

    Article  PubMed  PubMed Central  Google Scholar 

  62. Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, Beneke J, Pudney J, Anderson DJ, Ganem D, Haase AT (1997) Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71(1):715–719

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Dittmer DP, Richards KL, Damania B (2012) Treatment of Kaposi sarcoma-associated herpesvirus-associated cancers. Front Microbiol 3:141. https://doi.org/10.3389/fmicb.2012.00141

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. McClure LV, Sullivan CS (2008) Kaposi’s sarcoma herpes virus taps into a host microRNA regulatory network. Cell Host Microbe 3(1):1–3. https://doi.org/10.1016/j.chom.2007.12.002

    Article  PubMed  CAS  Google Scholar 

  65. Lu J, Jha HC, Verma SC, Sun Z, Banerjee S, Dzeng R, Robertson ES (2014) Kaposi’s sarcoma-associated herpesvirus-encoded LANA contributes to viral latent replication by activating phosphorylation of survivin. J Virol 88(8):4204–4217. https://doi.org/10.1128/JVI.03855-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Domsic JF, Chen HS, Lu F, Marmorstein R, Lieberman PM (2013) Molecular basis for oligomeric-DNA binding and episome maintenance by KSHV LANA. PLoS Pathog 9(10):e1003672. https://doi.org/10.1371/journal.ppat.1003672

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Hellert J, Weidner-Glunde M, Krausze J, Richter U, Adler H, Fedorov R, Pietrek M, Ruckert J, Ritter C, Schulz TF, Luhrs T (2013) A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins. PLoS Pathog 9(10):e1003640. https://doi.org/10.1371/journal.ppat.1003640

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Hellert J, Weidner-Glunde M, Krausze J, Lunsdorf H, Ritter C, Schulz TF, Luhrs T (2015) The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA. Proc Natl Acad Sci USA 112(21):6694–6699. https://doi.org/10.1073/pnas.1421804112

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  69. Correia B, Cerqueira SA, Beauchemin C, Pires de Miranda M, Li S, Ponnusamy R, Rodrigues L, Schneider TR, Carrondo MA, Kaye KM, Simas JP, McVey CE (2013) Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency. PLoS Pathog 9(10):e1003673. https://doi.org/10.1371/journal.ppat.1003673

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Groves AK, Cotter MA, Subramanian C, Robertson ES (2001) The latency-associated nuclear antigen encoded by Kaposi’s sarcoma-associated herpesvirus activates two major essential Epstein-Barr virus latent promoters. J Virol 75(19):9446–9457. https://doi.org/10.1128/JVI.75.19.9446-9457.2001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. An FQ, Folarin HM, Compitello N, Roth J, Gerson SL, McCrae KR, Fakhari FD, Dittmer DP, Renne R (2006) Long-term-infected telomerase-immortalized endothelial cells: a model for Kaposi’s sarcoma-associated herpesvirus latency in vitro and in vivo. J Virol 80(10):4833–4846

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. An FQ, Compitello N, Horwitz E, Sramkoski M, Knudsen ES, Renne R (2005) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest. J Biol Chem 280(5):3862–3874

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Department of Biotechnology of the Government of India (BT/PR15109/GBD/27/320/2011), an MRP Grant from UGC (FN-41-1144/2012), an R&D Grant from the University of Delhi, and a PURSE Grant from DST. NG is a project fellow funded by UGC.

Author information

Author notes

  1. Tanvi Tikla

    Present address: Hannover Medical School, Hannover, Germany

Authors and Affiliations

  1. Department of Microbiology, University of Delhi, South Campus, New Delhi, India

    Nivedita Gaur, Tanvi Tikla & Rajeev Kaul

Authors
  1. Nivedita Gaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tanvi Tikla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rajeev Kaul
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajeev Kaul.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Handling Editor: Scott Schmid.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gaur, N., Tikla, T. & Kaul, R. Kaposi sarcoma-associated herpes virus (KSHV) latent protein LANA modulates cellular genes associated with epithelial-to-mesenchymal transition. Arch Virol 164, 91–104 (2019). https://doi.org/10.1007/s00705-018-4060-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-018-4060-y

Search

Navigation