Abstract
Herpesviruses, polyomaviruses, and papillomaviruses have all been detected in glioblastoma cells and/or cell lines. Our group first published evidence of human cytomegalovirus (CMV), a herpesvirus, in glioblastoma specimens from immunocompetent patients in 2002. However, the discovery of CMV and other viruses in glioblastoma has met with controversy following several studies that failed to detect viral particles in GBM. Here we summarize the known relationships between viruses and malignant gliomas, including viral detection in GBM, the oncomodulatory effects of GBM-associated viruses, and the novel ways by which investigators are targeting viruses for the treatment of glioblastoma.
Keywords
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- BKV:
-
B.K. virus
- CNS:
-
Central nervous system
- CMV:
-
Cytomegalovirus
- DC:
-
Dendritic cell
- EBV:
-
Epstein-Barr virus
- GBM:
-
Glioblastoma
- HHV:
-
Human herpesvirus
- HPV:
-
Human papillomavirus
- IE:
-
Immediate-early
- JCV:
-
John Cunningham virus
- Tag:
-
Large tumor antigen
- MGMT:
-
O6-Methylguanine-DNA-methyltransferase
- pp:
-
Phosphoprotein
- PDGFRα:
-
Platelet-derived growth factor receptor alpha
- rGBM:
-
Recurrent GBM
- SV40:
-
Simian virus 40
- tag:
-
Small tumor antigen
- TMZ:
-
Temozolomide
References
Zhang AS, Ostrom QT, Kruchko C, Rogers L, Peereboom DM, Barnholtz-Sloan JS (2016) Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010. Neuro-Oncology. https://doi.org/10.1093/neuonc/now252
Stewart B, Wild CP (2014) World cancer report 2014
Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4(4):296–307. https://doi.org/10.1038/nrc1319
Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2016) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncology 18(suppl_5):v1–v75. https://doi.org/10.1093/neuonc/now207
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. https://doi.org/10.1056/NEJMoa043330
Parkin DM (2006) The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118(12):3030–3044. https://doi.org/10.1002/ijc.21731
Cimino PJ, Zhao G, Wang D, Sehn JK, Lewis JS Jr, Duncavage EJ (2014) Detection of viral pathogens in high grade gliomas from unmapped next-generation sequencing data. Exp Mol Pathol 96(3):310–315. https://doi.org/10.1016/j.yexmp.2014.03.010
Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, Nabors LB, Cobbs CG, Britt WJ (2002) Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res 62(12):3347–3350
Lucas KG, Bao L, Bruggeman R, Dunham K, Specht C (2011) The detection of CMV pp65 and IE1 in glioblastoma multiforme. J Neuro-Oncol 103(2):231–238. https://doi.org/10.1007/s11060-010-0383-6
Rahbar A, Stragliotto G, Orrego A, Peredo I, Taher C, Willems J, Soderberg-Naucler C (2012) Low levels of human cytomegalovirus infection in glioblastoma multiforme associates with patient survival − a case-control study. Herpesviridae 3:3. https://doi.org/10.1186/2042-4280-3-3
Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R (2008) Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol 116(1):79–86. https://doi.org/10.1007/s00401-008-0359-1
Chi J, Gu B, Zhang C, Peng G, Zhou F, Chen Y, Zhang G, Guo Y, Guo D, Qin J, Wang J, Li L, Wang F, Liu G, Xie F, Feng D, Zhou H, Huang X, Lu S, Liu Y, Hu W, Yao K (2012) Human herpesvirus 6 latent infection in patients with glioma. J Infect Dis 206(9):1394–1398. https://doi.org/10.1093/infdis/jis513
Cuomo L, Trivedi P, Cardillo MR, Gagliardi FM, Vecchione A, Caruso R, Calogero A, Frati L, Faggioni A, Ragona G (2001) Human herpesvirus 6 infection in neoplastic and normal brain tissue. J Med Virol 63(1):45–51
Luppi M, Barozzi P, Maiorana A, Marasca R, Trovato R, Fano R, Ceccherini-Nelli L, Torelli G (1995) Human herpesvirus-6: a survey of presence and distribution of genomic sequences in normal brain and neuroglial tumors. J Med Virol 47(1):105–111
Caldarelli-Stefano R, Boldorini R, Monga G, Meraviglia E, Zorini EO, Ferrante P (2000) JC virus in human glial-derived tumors. Hum Pathol 31(3):394–395
Huang H, Reis R, Yonekawa Y, Lopes JM, Kleihues P, Ohgaki H (1999) Identification in human brain tumors of DNA sequences specific for SV40 large T antigen. Brain Pathol 9(1):33–42
Kouhata T, Fukuyama K, Hagihara N, Tabuchi K (2001) Detection of simian virus 40 DNA sequence in human primary glioblastomas multiforme. J Neurosurg 95(1):96–101. https://doi.org/10.3171/jns.2001.95.1.0096
Martini F, Iaccheri L, Lazzarin L, Carinci P, Corallini A, Gerosa M, Iuzzolino P, Barbanti-Brodano G, Tognon M (1996) SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. Cancer Res 56(20):4820–4825
Rollison DE, Utaipat U, Ryschkewitsch C, Hou J, Goldthwaite P, Daniel R, Helzlsouer KJ, Burger PC, Shah KV, Major EO (2005) Investigation of human brain tumors for the presence of polyomavirus genome sequences by two independent laboratories. Int J Cancer 113(5):769–774. https://doi.org/10.1002/ijc.20641
Boldorini R, Pagani E, Car PG, Omodeo-Zorini E, Borghi E, Tarantini L, Bellotti C, Ferrante P, Monga G (2003) Molecular characterisation of JC virus strains detected in human brain tumours. Pathology 35(3):248–253
Del Valle L, Gordon J, Assimakopoulou M, Enam S, Geddes JF, Varakis JN, Katsetos CD, Croul S, Khalili K (2001) Detection of JC virus DNA sequences and expression of the viral regulatory protein T-antigen in tumors of the central nervous system. Cancer Res 61(10):4287–4293
Munoz-Marmol AM, Mola G, Ruiz-Larroya T, Fernandez-Vasalo A, Vela E, Mate JL, Ariza A (2006) Rarity of JC virus DNA sequences and early proteins in human gliomas and medulloblastomas: the controversial role of JC virus in human neurooncogenesis. Neuropathol Appl Neurobiol 32(2):131–140. https://doi.org/10.1111/j.1365-2990.2006.00711.x
Corallini A, Pagnani M, Viadana P, Silini E, Mottes M, Milanesi G, Gerna G, Vettor R, Trapella G, Silvani V et al (1987) Association of BK virus with human brain tumors and tumors of pancreatic islets. Int J Cancer 39(1):60–67
Negrini M, Rimessi P, Mantovani C, Sabbioni S, Corallini A, Gerosa MA, Barbanti-Brodano G (1990) Characterization of BK virus variants rescued from human tumours and tumour cell lines. J Gen Virol 71(Pt 11):2731–2736. https://doi.org/10.1099/0022-1317-71-11-2731
Cohen JI, Fauci AS, Varmus H, Nabel GJ (2011) Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med 3(107):107fs107. https://doi.org/10.1126/scitranslmed.3002878
Bate SL, Dollard SC, Cannon MJ (2010) Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988–2004. Clin Infect Dis 50(11):1439–1447. https://doi.org/10.1086/652438
Sinclair J, Sissons P (2006) Latency and reactivation of human cytomegalovirus. J Gen Virol 87(Pt 7):1763–1779. https://doi.org/10.1099/vir.0.81891-0
Bianchi E, Roncarati P, Hougrand O, Guerin-El Khourouj V, Boreux R, Kroonen J, Martin D, Robe P, Rogister B, Delvenne P, Deprez M (2015) Human cytomegalovirus and primary intracranial tumours: frequency of tumour infection and lack of correlation with systemic immune anti-viral responses. Neuropathol Appl Neurobiol 41(2):e29–e40. https://doi.org/10.1111/nan.12172
Harkins L, Volk AL, Samanta M, Mikolaenko I, Britt WJ, Bland KI, Cobbs CS (2002) Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet 360(9345):1557–1563. https://doi.org/10.1016/S0140-6736(02)11524-8
Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS (2003) High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol 170(3):998–1002. https://doi.org/10.1097/01.ju.0000080263.46164.97
Zafiropoulos A, Tsentelierou E, Billiri K, Spandidos DA (2003) Human herpes viruses in non-melanoma skin cancers. Cancer Lett 198(1):77–81
Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, Sampson JH (2008) Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro-Oncology 10(1):10–18. https://doi.org/10.1215/15228517-2007-035
Rahbar A, Orrego A, Peredo I, Dzabic M, Wolmer-Solberg N, Straat K, Stragliotto G, Soderberg-Naucler C (2013) Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival. J Clin Virol 57(1):36–42. https://doi.org/10.1016/j.jcv.2012.12.018
Baumgarten P, Michaelis M, Rothweiler F, Starzetz T, Rabenau HF, Berger A, Jennewein L, Braczynski AK, Franz K, Seifert V, Steinbach JP, Allwinn R, Mittelbronn M, Cinatl J Jr (2014) Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics. Neuro-Oncology 16(11):1469–1477. https://doi.org/10.1093/neuonc/nou167
Holdhoff M, Guner G, Rodriguez FJ, Hicks JL, Zheng Q, Forman MS, Ye X, Grossman SA, Meeker AK, Heaphy CM, Eberhart CG, De Marzo AM, Arav-Boger R (2016) Absence of cytomegalovirus in glioblastoma and other high-grade gliomas by real-time PCR, immunohistochemistry, and in situ hybridization. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-16-1490
Strong MJ, Et B, Lin Z, Morris CA, Baddoo M, Taylor CM, Ware ML, Flemington EK (2016) A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus – tumor association. Acta Neuropathol Commun 4(1):71. https://doi.org/10.1186/s40478-016-0338-z
Ablashi DV, Lusso P, Hung CL, Salahuddin SZ, Josephs SF, Llana T, Kramarsky B, Biberfeld P, Markham PD, Gallo RC (1988) Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6). Int J Cancer 42(5):787–791
Levy JA, Ferro F, Lennette ET, Oshiro L, Poulin L (1990) Characterization of a new strain of HHV-6 (HHV-6SF) recovered from the saliva of an HIV-infected individual. Virology 178(1):113–121
Tedder RS, Briggs M, Cameron CH, Honess R, Robertson D, Whittle H (1987) A novel lymphotropic herpesvirus. Lancet 2(8555):390–392
Crawford JR, Santi MR, Cornelison R, Sallinen SL, Haapasalo H, MacDonald TJ (2009) Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors. J Neuro-Oncol 95(1):49–60. https://doi.org/10.1007/s11060-009-9908-2
Colvin EK, Weir C, Ikin RJ, Hudson AL (2014) SV40 TAg mouse models of cancer. Semin Cell Dev Biol 27:61–73. https://doi.org/10.1016/j.semcdb.2014.02.004
Kirschstein RL, Gerber P (1962) Ependymomas produced after intracerebral inoculation of SV40 into new-born hamsters. Nature 195:299–300
Ray FA, Peabody DS, Cooper JL, Cram LS, Kraemer PM (1990) SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts. J Cell Biochem 42(1):13–31. https://doi.org/10.1002/jcb.240420103
Engels EA, Katki HA, Nielsen NM, Winther JF, Hjalgrim H, Gjerris F, Rosenberg PS, Frisch M (2003) Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40. J Natl Cancer Inst 95(7):532–539
Fisher SG, Weber L, Carbone M (1999) Cancer risk associated with simian virus 40 contaminated polio vaccine. Anticancer Res 19(3B):2173–2180
Vilchez RA, Kozinetz CA, Arrington AS, Madden CR, Butel JS (2003) Simian virus 40 in human cancers. Am J Med 114(8):675–684
Scherneck S, Rudolph M, Geissler E, Vogel F, Lubbe L, Wahlte H, Nisch G, Weickmann F, Zimmermann W (1979) Isolation of a SV40-like Papovavirus from a human glioblastoma. Int J Cancer 24(5):523–531
Suzuki SO, Mizoguchi M, Iwaki T (1997) Detection of SV40 T antigen genome in human gliomas. Brain Tumor Pathol 14(2):125–129
Shah K (1996) Polyomaviruses. Fields Virol 2:2027–2043
Gordon J, Krynska B, Otte J, Houff SA, Khalili K (1998) Oncogenic potential of human neurotropic papovavirus, JCV, in CNS. Dev Biol Stand 94:93–101
Darbinyan A, Kaminski R, White MK, Darbinian-Sarkissian N, Khalili K (2013) Polyomavirus JC infection inhibits differentiation of oligodendrocyte progenitor cells. J Neurosci Res 91(1):116–127. https://doi.org/10.1002/jnr.23135
Wuthrich C, Batson S, Anderson MP, White LR, Koralnik IJ (2016) JC Virus infects neurons and glial cells in the hippocampus. J Neuropathol Exp Neurol. https://doi.org/10.1093/jnen/nlw050
Imperiale MJ (2000) The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology 267(1):1–7. https://doi.org/10.1006/viro.1999.0092
Pina-Oviedo S, De Leon-Bojorge B, Cuesta-Mejias T, White MK, Ortiz-Hidalgo C, Khalili K, Del Valle L (2006) Glioblastoma multiforme with small cell neuronal-like component: association with human neurotropic JC virus. Acta Neuropathol 111(4):388–396. https://doi.org/10.1007/s00401-006-0050-3
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
Vidone M, Alessandrini F, Marucci G, Farnedi A, de Biase D, Ricceri F, Calabrese C, Kurelac I, Porcelli AM, Cricca M, Gasparre G (2014) Evidence of association of human papillomavirus with prognosis worsening in glioblastoma multiforme. Neuro-Oncology 16(2):298–302. https://doi.org/10.1093/neuonc/not140
Varakis J, ZuRhein GM, Padgett BL, Walker DL (1978) Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, a human polyoma virus. Cancer Res 38(6):1718–1722
Walker DL, Padgett BL, ZuRhein GM, Albert AE, Marsh RF (1973) Human papovavirus (JC): induction of brain tumors in hamsters. Science 181(4100):674–676
Darbinian N, Gallia GL, King J, Del Valle L, Johnson EM, Khalili K (2001) Growth inhibition of glioblastoma cells by human Pur(alpha). J Cell Physiol 189(3):334–340. https://doi.org/10.1002/jcp.10029
Dyson N, Bernards R, Friend SH, Gooding LR, Hassell JA, Major EO, Pipas JM, Vandyke T, Harlow E (1990) Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol 64(3):1353–1356
Dyson N, Buchkovich K, Whyte P, Harlow E (1989) The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus. Cell 58(2):249–255
Harris KF, Christensen JB, Imperiale MJ (1996) BK virus large T antigen: interactions with the retinoblastoma family of tumor suppressor proteins and effects on cellular growth control. J Virol 70(4):2378–2386
Pipas JM (1992) Common and unique features of T antigens encoded by the polyomavirus group. J Virol 66(7):3979–3985
Sariyer IK, Sariyer R, Otte J, Gordon J (2016) Pur-alpha induces JCV gene expression and viral replication by suppressing SRSF1 in glial cells. PLoS One 11(6):e0156819. https://doi.org/10.1371/journal.pone.0156819
Sullivan CS, Tremblay JD, Fewell SW, Lewis JA, Brodsky JL, Pipas JM (2000) Species-specific elements in the large T-antigen J domain are required for cellular transformation and DNA replication by simian virus 40. Mol Cell Biol 20(15):5749–5757
Stewart N, Bacchetti S (1991) Expression of SV40 large T antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells. Virology 180(1):49–57
Trabanelli C, Corallini A, Gruppioni R, Sensi A, Bonfatti A, Campioni D, Merlin M, Calza N, Possati L, Barbanti-Brodano G (1998) Chromosomal aberrations induced by BK virus T antigen in human fibroblasts. Virology 243(2):492–496. https://doi.org/10.1006/viro.1998.9080
Khalili K, Del Valle L, Otte J, Weaver M, Gordon J (2003) Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene 22(33):5181–5191. https://doi.org/10.1038/sj.onc.1206559
Kashanchi F, Araujo J, Doniger J, Muralidhar S, Hoch R, Khleif S, Mendelson E, Thompson J, Azumi N, Brady JN, Luppi M, Torelli G, Rosenthal LJ (1997) Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53. Oncogene 14(3):359–367. https://doi.org/10.1038/sj.onc.1200840
Wang X, Hu M, Xing F, Wang M, Wang B, Qian D (2017) Human cytomegalovirus infection promotes the stemness of U251 glioma cells. J Med Virol 89(5):878–886. https://doi.org/10.1002/jmv.24708
Cobbs CS, Soroceanu L, Denham S, Zhang W, Kraus MH (2008) Modulation of oncogenic phenotype in human glioma cells by cytomegalovirus IE1-mediated mitogenicity. Cancer Res 68(3):724–730. https://doi.org/10.1158/0008-5472.CAN-07-2291
Lee K, Jeon K, Kim JM, Kim VN, Choi DH, Kim SU, Kim S (2005) Downregulation of GFAP, TSP-1, and p53 in human glioblastoma cell line, U373MG, by IE1 protein from human cytomegalovirus. Glia 51(1):1–12. https://doi.org/10.1002/glia.20179
Soroceanu L, Matlaf L, Khan S, Akhavan A, Singer E, Bezrookove V, Decker S, Ghanny S, Hadaczek P, Bengtsson H, Ohlfest J, Luciani-Torres MG, Harkins L, Perry A, Guo H, Soteropoulos P, Cobbs CS (2015) Cytomegalovirus immediate-early proteins promote stemness properties in glioblastoma. Cancer Res 75(15):3065–3076. https://doi.org/10.1158/0008-5472.CAN-14-3307
Fornara O, Bartek J Jr, Rahbar A, Odeberg J, Khan Z, Peredo I, Hamerlik P, Bartek J, Stragliotto G, Landazuri N, Soderberg-Naucler C (2016) Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact. Cell Death Differ 23(2):261–269. https://doi.org/10.1038/cdd.2015.91
Matlaf LA, Harkins LE, Bezrookove V, Cobbs CS, Soroceanu L (2013) Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro-angiogenic signaling by activation of stem cell factor. PLoS One 8(7):e68176. https://doi.org/10.1371/journal.pone.0068176
MacManiman JD, Meuser A, Botto S, Smith PP, Liu F, Jarvis MA, Nelson JA, Caposio P (2014) Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis. MBio 5(6):e02035. https://doi.org/10.1128/mBio.02035-14
Soroceanu L, Matlaf L, Bezrookove V, Harkins L, Martinez R, Greene M, Soteropoulos P, Cobbs CS (2011) Human cytomegalovirus US28 found in glioblastoma promotes an invasive and angiogenic phenotype. Cancer Res 71(21):6643–6653. https://doi.org/10.1158/0008-5472.CAN-11-0744
Ulasov IV, Kaverina NV, Ghosh D, Baryshnikova MA, Kadagidze ZG, Karseladze AI, Baryshnikov AY, Cobbs CS (2017) CMV70-3P miRNA contributes to the CMV mediated glioma stemness and represents a target for glioma experimental therapy. Oncotarget 8(16):25989–25999. https://doi.org/10.18632/oncotarget.11175
Cobbs C, Khan S, Matlaf L, McAllister S, Zider A, Yount G, Rahlin K, Harkins L, Bezrookove V, Singer E, Soroceanu L (2014) HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and invasiveness via PDGFR-alpha activation. Oncotarget 5(4):1091–1100. https://doi.org/10.18632/oncotarget.1787
Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, Alvarez-Buylla A (2006) PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51(2):187–199. https://doi.org/10.1016/j.neuron.2006.06.012
Moens U, Van Ghelue M, Ehlers B (2014) Are human polyomaviruses co-factors for cancers induced by other oncoviruses? Rev Med Virol 24(5):343–360. https://doi.org/10.1002/rmv.1798
Gorman CM, Gies D, McCray G, Huang M (1989) The human cytomegalovirus major immediate early promoter can be trans-activated by adenovirus early proteins. Virology 171(2):377–385
Yoshikawa T, Asano Y, Akimoto S, Ozaki T, Iwasaki T, Kurata T, Goshima F, Nishiyama Y (2002) Latent infection of human herpesvirus 6 in astrocytoma cell line and alteration of cytokine synthesis. J Med Virol 66(4):497–505
Winklhofer KF, Albrecht I, Wegner M, Heilbronn R (2000) Human cytomegalovirus immediate-early gene 2 expression leads to JCV replication in nonpermissive cells via transcriptional activation of JCV T antigen. Virology 275(2):323–334. https://doi.org/10.1006/viro.2000.0503
Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7(3):211–217. https://doi.org/10.1016/j.ccr.2005.02.013
Rakoff-Nahoum S (2006) Why cancer and inflammation? Yale. J Biol Med 79(3–4):123–130
Smith PD, Saini SS, Raffeld M, Manischewitz JF, Wahl SM (1992) Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. J Clin Invest 90(5):1642–1648. https://doi.org/10.1172/JCI116035
Avdic S, McSharry BP, Steain M, Poole E, Sinclair J, Abendroth A, Slobedman B (2016) Human cytomegalovirus-encoded human interleukin-10 (IL-10) homolog amplifies its immunomodulatory potential by upregulating human IL-10 in monocytes. J Virol 90(8):3819–3827. https://doi.org/10.1128/JVI.03066-15
Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT (2013) Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res 19(12):3165–3175. https://doi.org/10.1158/1078-0432.CCR-12-3314
Dziurzynski K, Wei J, Qiao W, Hatiboglu MA, Kong LY, Wu A, Wang Y, Cahill D, Levine N, Prabhu S, Rao G, Sawaya R, Heimberger AB (2011) Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res 17(14):4642–4649. https://doi.org/10.1158/1078-0432.CCR-11-0414
Huettner C, Czub S, Kerkau S, Roggendorf W, Tonn JC (1997) Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro. Anticancer Res 17(5A):3217–3224
Spencer JV, Lockridge KM, Barry PA, Lin G, Tsang M, Penfold ME, Schall TJ (2002) Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10. J Virol 76(3):1285–1292
Farrell HE, Vally H, Lynch DM, Fleming P, Shellam GR, Scalzo AA, Davis-Poynter NJ (1997) Inhibition of natural killer cells by a cytomegalovirus MHC class I homologue in vivo. Nature 386(6624):510–514. https://doi.org/10.1038/386510a0
Hegde NR, Tomazin RA, Wisner TW, Dunn C, Boname JM, Lewinsohn DM, Johnson DC (2002) Inhibition of HLA-DR assembly, transport, and loading by human cytomegalovirus glycoprotein US3: a novel mechanism for evading major histocompatibility complex class II antigen presentation. J Virol 76(21):10929–10941
Odeberg J, Plachter B, Branden L, Soderberg-Naucler C (2003) Human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR alpha-chain. Blood 101(12):4870–4877. https://doi.org/10.1182/blood-2002-05-1504
Tomazin R, Boname J, Hegde NR, Lewinsohn DM, Altschuler Y, Jones TR, Cresswell P, Nelson JA, Riddell SR, Johnson DC (1999) Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. Nat Med 5(9):1039–1043. https://doi.org/10.1038/12478
Li L, Chi J, Zhou F, Guo D, Wang F, Liu G, Zhang C, Yao K (2010) Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway. J Biomed Res 24(6):444–451. https://doi.org/10.1016/S1674-8301(10)60059-0
Wang F, Yao K, Yin QZ, Zhou F, Ding CL, Peng GY, Xu J, Chen Y, Feng DJ, Ma CL, Xu WR (2006) Human herpesvirus-6-specific interleukin 10-producing CD4+ T cells suppress the CD4+ T-cell response in infected individuals. Microbiol Immunol 50(10):787–803
Hadaczek P, Ozawa T, Soroceanu L, Yoshida Y, Matlaf L, Singer E, Fiallos E, James CD, Cobbs CS (2013) Cidofovir: a novel antitumor agent for glioblastoma. Clin Cancer Res 19(23):6473–6483. https://doi.org/10.1158/1078-0432.CCR-13-1121
Stragliotto G, Rahbar A, Solberg NW, Lilja A, Taher C, Orrego A, Bjurman B, Tammik C, Skarman P, Peredo I, Soderberg-Naucler C (2013) Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 133(5):1204–1213. https://doi.org/10.1002/ijc.28111
Liu CJ, Hu YW (2014) Immortal time bias in retrospective analysis: is there a survival benefit in patients with glioblastoma who received prolonged treatment of adjuvant valganciclovir? Int J Cancer 135(1):250–251. https://doi.org/10.1002/ijc.28664
Soderberg-Naucler C, Peredo I, Rahbar A, Hansson F, Nordlund A, Stragliotto G (2014) Use of Cox regression with treatment status as a time-dependent covariate to re-analyze survival benefit excludes immortal time bias effect in patients with glioblastoma who received prolonged adjuvant treatment with valganciclovir. Int J Cancer 135(1):248–249. https://doi.org/10.1002/ijc.28663
Ghazi A, Ashoori A, Hanley PJ, Brawley VS, Shaffer DR, Kew Y, Powell SZ, Grossman R, Grada Z, Scheurer ME, Hegde M, Leen AM, Bollard CM, Rooney CM, Heslop HE, Gottschalk S, Ahmed N (2012) Generation of polyclonal CMV-specific T cells for the adoptive immunotherapy of glioblastoma. J Immunother 35(2):159–168. https://doi.org/10.1097/CJI.0b013e318247642f
Nair SK, De Leon G, Boczkowski D, Schmittling R, Xie W, Staats J, Liu R, Johnson LA, Weinhold K, Archer GE, Sampson JH, Mitchell DA (2014) Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells. Clin Cancer Res 20(10):2684–2694. https://doi.org/10.1158/1078-0432.CCR-13-3268
Batich KA, Reap EA, Archer GE, Sanchez-Perez L, Nair SK, Schmittling RJ, Norberg P, Xie W, Herndon JE II, Healy P, McLendon RE, Friedman AH, Friedman HS, Bigner D, Vlahovic G, Mitchell DA, Sampson JH (2017) Long-term survival in glioblastoma with cytomegalovirus pp65-targeted vaccination. Clin Cancer Res 23(8):1898–1909. https://doi.org/10.1158/1078-0432.CCR-16-2057
Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A, Friedman AH, Friedman HS, Herndon JE II, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Sampson JH (2015) Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature 519(7543):366–369. https://doi.org/10.1038/nature14320
Crough T, Beagley L, Smith C, Jones L, Walker DG, Khanna R (2012) Ex vivo functional analysis, expansion and adoptive transfer of cytomegalovirus-specific T-cells in patients with glioblastoma multiforme. Immunol Cell Biol 90(9):872–880. https://doi.org/10.1038/icb.2012.19
Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S, Matthews K, Jones L, Crough T, Dasari V, Klein K, Smalley A, Alexander H, Walker DG, Khanna R (2014) Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 74(13):3466–3476. https://doi.org/10.1158/0008-5472.CAN-14-0296
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Foster, H., Cobbs, C.S. (2019). Viruses and Glioblastoma: Affliction or Opportunity?. In: Robertson, E. (eds) Microbiome and Cancer. Current Cancer Research. Humana Press, Cham. https://doi.org/10.1007/978-3-030-04155-7_4
Download citation
DOI: https://doi.org/10.1007/978-3-030-04155-7_4
Published:
Publisher Name: Humana Press, Cham
Print ISBN: 978-3-030-04154-0
Online ISBN: 978-3-030-04155-7
eBook Packages: MedicineMedicine (R0)