Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Archives of Virology
Published in: Archives of Virology 10/2018

01-10-2018 | Review

Cellular and viral oncogenes: the key to unlocking unknowns of Kaposi’s sarcoma-associated herpesvirus pathogenesis

Authors: Hosni A. M. Hussein, Ikenna B. Okafor, Lia R. Walker, Usama M. Abdel-Raouf, Shaw M. Akula

Published in: Archives of Virology | Issue 10/2018

Login to get access

Abstract

Oncogenic viruses carry an extensive arsenal of oncogenes for hijacking cellular pathways. Notably, variations in oncogenes among tumor-producing viruses give rise to different mechanisms for cellular transformation. Specifically, Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic virus able to infect and transform a variety of cell types. The oncogenicity of KSHV disseminates from the virus’ ability to induce and encode a wide variety of both cellular and viral oncogenes. Such an array of cellular and viral oncogenes enables KSHV to induce the malignant phenotype of a KSHV-associated cancer. Evolutionarily, KSHV has acquired many oncogenic homologues capable of inducing cell proliferation, cell differentiation, cell survival, and immune evasion. Integration between inducing and encoding oncogenes plays a vital role in KSHV pathogenicity. KSHV is alleged to harbor the highest number of potential oncogenes by which a virus promotes cellular transformation and malignancy. Many KSHV inducing/encoding oncogenes are mainly expressed during the latent phase of KSHV infection, a period required for virus establishment of malignant cellular transformation. Elucidation of the exact mechanism(s) by which oncogenes promote KSHV pathogenicity would not only give rise to potential novel therapeutic targets/drugs but would also add to our understanding of cancer biology. The scope of this review is to examine the roles of the most important cellular and viral oncogenes involved in KSHV pathogenicity.
Literature
1.
Abere B, Schulz TF (2016) KSHV non-structural membrane proteins involved in the activation of intracellular signaling pathways and the pathogenesis of Kaposi’s sarcoma. Curr Opin Virol 20:11–19PubMedCrossRef
2.
3.
Akula SM, Ford PW, Whitman AG, Hamden KE, Shelton JG, McCubrey JA (2004) Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection. Oncogene 23:5227–5241PubMedCrossRef
4.
An J, Sun Y, Sun R, Rettig MB (2003) Kaposi’s sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene 22:3371–3385PubMedCrossRef
5.
Aoki Y, Jaffe ES, Chang Y, Jones K, Teruya-Feldstein J, Moore PS, Tosato G (1999) Angiogenesis and hematopoiesis induced by Kaposi’s sarcoma-associated herpesvirus-encoded interleukin-6. Blood 93:4034–4043PubMed
6.
Arias C, Weisburd B, Stern-Ginossar N, Mercier A, Madrid AS, Bellare P, Holdorf M, Weissman JS, Ganem D (2014) KSHV 2.0: a comprehensive annotation of the Kaposi’s sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLoS Pathog 10:e1003847PubMedPubMedCentralCrossRef
7.
Bais C, Van Geelen A, Eroles P, Mutlu A, Chiozzini C, Dias S, Silverstein RL, Rafii S, Mesri EA (2003) Kaposi’s sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell 3:131–143PubMedCrossRef
8.
Ballestas ME, Chatis PA, Kaye KM (1999) Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284:641–644PubMedCrossRef
9.
Ballon G, Chen K, Perez R, Tam W, Cesarman E (2011) Kaposi sarcoma herpesvirus (KSHV) vFLIP oncoprotein induces B cell transdifferentiation and tumorigenesis in mice. J Clin Invest 121:1141–1153PubMedPubMedCentralCrossRef
10.
Baresova P, Pitha PM, Lubyova B (2013) Distinct roles of Kaposi’s sarcoma-associated herpesvirus-encoded viral interferon regulatory factors in inflammatory response and cancer. J Virol 87:9398–9410PubMedPubMedCentralCrossRef
11.
Bieleski L, Talbot SJ (2001) Kaposi’s sarcoma-associated herpesvirus vCyclin open reading frame contains an internal ribosome entry site. J Virol 75:1864–1869PubMedPubMedCentralCrossRef
12.
13.
Bogenberger J, Whatcott C, Hansen N, Delman D, Shi CX, Kim W, Haws H, Soh K, Lee YS, Peterson P, Siddiqui-Jain A, Weitman S, Stewart K, Bearss D, Mesa R, Warner S, Tibes R (2017) Combined venetoclax and alvocidib in acute myeloid leukemia. Oncotarget 8:107206–107222PubMedPubMedCentralCrossRef
14.
Boissan M, Feger F, Guillosson JJ, Arock M (2000) c-Kit and c-kit mutations in mastocytosis and other hematological diseases. J Leukoc Biol 67:135–148PubMedCrossRef
15.
Bottero V, Sharma-Walia N, Kerur N, Paul AG, Sadagopan S, Cannon M, Chandran B (2009) Kaposi sarcoma-associated herpes virus (KSHV) G protein-coupled receptor (vGPCR) activates the ORF50 lytic switch promoter: a potential positive feedback loop for sustained ORF50 gene expression. Virology 392:34–51PubMedPubMedCentralCrossRef
16.
Bowser BS, DeWire SM, Damania B (2002) Transcriptional regulation of the K1 gene product of Kaposi’s sarcoma-associated herpesvirus. J Virol 76:12574–12583PubMedPubMedCentralCrossRef
17.
Brison O (1993) Gene amplification and tumor progression. Biochim Biophys Acta 1155:25–41PubMed
18.
Broecker F, Hardt C, Herwig R, Timmermann B, Kerick M, Wunderlich A, Schweiger MR, Borsig L, Heikenwalder M, Lehrach H, Moelling K (2016) Transcriptional signature induced by a C-terminal c-Src mutant in a human breast cell line. FEBS J 283:1669–1688PubMedCrossRef
19.
Brown MT, Cooper JA (1996) Regulation, substrates and functions of src. Biochim Biophys Acta 1287:121–149PubMed
20.
Cai Q, Verma SC, Lu J, Robertson ES (2010) Molecular biology of Kaposi’s sarcoma-associated herpesvirus and related oncogenesis. Adv Virus Res 78:87–142PubMedPubMedCentralCrossRef
21.
Cai Q, Xiao B, Si H, Cervini A, Gao J, Lu J, Upadhyay SK, Verma SC, Robertson ES (2012) Kaposi’s sarcoma herpesvirus upregulates Aurora A expression to promote p53 phosphorylation and ubiquitylation. PLoS Pathog 8:e1002566PubMedPubMedCentralCrossRef
22.
Cao Y, Minhas V, Tan X, Huang J, Wang B, Zhu M, Gao Y, Zhao T, Yang L, Wood C (2014) High prevalence of early childhood infection by Kaposi’s sarcoma-associated herpesvirus in a minority population in China. Clin Microbiol Infect 20:475–481PubMedCrossRef
23.
Carroll PA, Kenerson HL, Yeung RS, Lagunoff M (2006) Latent Kaposi’s sarcoma-associated herpesvirus infection of endothelial cells activates hypoxia-induced factors. J Virol 80:10802–10812PubMedPubMedCentralCrossRef
24.
Cavallin LE, Goldschmidt-Clermont P, Mesri EA (2014) Molecular and cellular mechanisms of KSHV oncogenesis of Kaposi’s sarcoma associated with HIV/AIDS. PLoS Pathog 10:e1004154PubMedPubMedCentralCrossRef
25.
Cesarman E, Nador RG, Bai F, Bohenzky RA, Russo JJ, Moore PS, Chang Y, Knowles DM (1996) Kaposi’s sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi’s sarcoma and malignant lymphoma. J Virol 70:8218–8223PubMedPubMedCentral
26.
Cha S, Choe J, Seo T (2016) vIRF3 encoded by Kaposi’s sarcoma-associated herpesvirus inhibits T-cell factor-dependent transcription via a CREB-binding protein-interaction motif. Biochem Biophys Res Commun 479:697–702PubMedCrossRef
27.
Chaft JE, Arcila ME, Paik PK, Lau C, Riely GJ, Pietanza MC, Zakowski MF, Rusch V, Sima CS, Ladanyi M, Kris MG (2012) Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther 11:485–491PubMedCrossRef
28.
Chandran B (2010) Early events in Kaposi’s sarcoma-associated herpesvirus infection of target cells. J Virol 84:2188–2199PubMedCrossRef
29.
Chandriani S, Ganem D (2010) Array-based transcript profiling and limiting-dilution reverse transcription-PCR analysis identify additional latent genes in Kaposi’s sarcoma-associated herpesvirus. J Virol 84:5565–5573PubMedPubMedCentralCrossRef
30.
Chang Y, Moore PS, Talbot SJ, Boshoff CH, Zarkowska T, Godden K, Paterson H, Weiss RA, Mittnacht S (1996) Cyclin encoded by KS herpesvirus. Nature 382:410PubMedCrossRef
31.
Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, Wilkie D, Carter CA, Taylor IC, Lynch M, Wilhelm S (2007) Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 59:561–574PubMedCrossRef
32.
Chaudhary PM, Jasmin A, Eby MT, Hood L (1999) Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins. Oncogene 18:5738–5746PubMedCrossRef
33.
Cheng EH, Nicholas J, Bellows DS, Hayward GS, Guo HG, Reitz MS, Hardwick JM (1997) A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci USA 94:690–694PubMedCrossRef
34.
Chiou CJ, Poole LJ, Kim PS, Ciufo DM, Cannon JS, ap Rhys CM, Alcendor DJ, Zong JC, Ambinder RF, Hayward GS (2002) Patterns of gene expression and a transactivation function exhibited by the vGCR (ORF74) chemokine receptor protein of Kaposi’s sarcoma-associated herpesvirus. J Virol 76:3421–3439PubMedPubMedCentralCrossRef
35.
Chmura JC, Herold K, Ruffin A, Atuobi T, Fabiyi Y, Mitchell AE, Choi YB, Ehrlich ES (2017) The Itch ubiquitin ligase is required for KSHV RTA induced vFLIP degradation. Virology 501:119–126PubMedCrossRef
36.
Choi YB, Nicholas J (2008) Autocrine and paracrine promotion of cell survival and virus replication by human herpesvirus 8 chemokines. J Virol 82:6501–6513PubMedPubMedCentralCrossRef
37.
Coffin JM (1976) Genes responsible for transformation by avian RNA tumor viruses. Cancer Res 36:4282–4288PubMed
38.
Cohen A, Brodie C, Sarid R (2006) An essential role of ERK signalling in TPA-induced reactivation of Kaposi’s sarcoma-associated herpesvirus. J Gen Virol 87:795–802PubMedCrossRef
39.
40.
Cuconati A, White E (2002) Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection. Genes Dev 16:2465–2478PubMedCrossRef
41.
Cunningham C, Barnard S, Blackbourn DJ, Davison AJ (2003) Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors. J Gen Virol 84:1471–1483PubMedCrossRef
42.
43.
44.
45.
Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, Gu W, Gautier J, Dalla-Favera R (2007) Non-transcriptional control of DNA replication by c-Myc. Nature 448:445–451PubMedCrossRef
46.
Faris M, Ensoli B, Kokot N, Nel AE (1998) Inflammatory cytokines induce the expression of basic fibroblast growth factor (bFGF) isoforms required for the growth of Kaposi’s sarcoma and endothelial cells through the activation of AP-1 response elements in the bFGF promoter. Aids 12:19–27PubMedCrossRef
47.
Fernandez-Figueras MT, Puig L, Fernandez-Vasalo A, Esquius M, Montero MA, Ariza A (2000) Immunohistochemical detection of Bcl-2 in Kaposi’s sarcoma lesions varies according to histopathologic stage, whereas expression of Bcl-x and Mcl-1 differs according to human immunodeficiency virus serologic status of patients. Mod Pathol 13:438–445PubMedCrossRef
48.
Field N, Low W, Daniels M, Howell S, Daviet L, Boshoff C, Collins M (2003) KSHV vFLIP binds to IKK-gamma to activate IKK. J Cell Sci 116:3721–3728PubMedCrossRef
49.
Filippakis H, Spandidos DA, Sourvinos G (2010) Herpesviruses: hijacking the Ras signaling pathway. Biochim Biophys Acta 1803:777–785PubMedCrossRef
50.
Ford PW, Bryan BA, Dyson OF, Weidner DA, Chintalgattu V, Akula SM (2006) Raf/MEK/ERK signalling triggers reactivation of Kaposi’s sarcoma-associated herpesvirus latency. J Gen Virol 87:1139–1144PubMedCrossRef
51.
Frixa T, Donzelli S, Blandino G (2015) Oncogenic MicroRNAs: key players in malignant transformation. Cancers (Basel) 7:2466–2485CrossRef
52.
Fu J, Liu Y, Wang X, Yuan B, Zhang Y (2017) Role of DHX33 in c-Myc-induced cancers. Carcinogenesis 38:649–660PubMedCrossRef
53.
Gallo A, Lampe M, Gunther T, Brune W (2017) The viral Bcl-2 homologs of Kaposi’s sarcoma-associated herpesvirus and rhesus rhadinovirus share an essential role for viral replication. J Virol 91:e01875-16PubMedPubMedCentralCrossRef
54.
Gan HK, Seruga B, Knox JJ (2009) Sunitinib in solid tumors. Expert Opin Investig Drugs 18:821–834PubMedCrossRef
55.
56.
Ganesh S, Shui X, Craig K, Koser M, Chopda GR, Cyr WA, Lai C, Dudek H, Wang W, Brown B, Abrams M (2018) β-catenin mRNA silencing and MEK inhibition display synergistic efficacy in preclinical tumor models. Mol Cancer Ther 17:544–553PubMedCrossRef
57.
58.
Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS (1997) KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 15:1979–1985PubMedCrossRef
59.
Gelgor A, Kalt I, Bergson S, Brulois KF, Jung JU, Sarid R (2015) Viral Bcl-2 encoded by the Kaposi’s sarcoma-associated herpesvirus is vital for virus reactivation. J Virol 89:5298–5307PubMedPubMedCentralCrossRef
60.
61.
Giffin L, West JA, Damania B (2015) Kaposi’s sarcoma-associated herpesvirus interleukin-6 modulates endothelial cell movement by upregulating cellular genes involved in migration. MBio 6:e01499–e01515PubMedPubMedCentralCrossRef
62.
Gramolelli S, Schulz TF (2015) The role of Kaposi sarcoma-associated herpesvirus in the pathogenesis of Kaposi sarcoma. J Pathol 235:368–380PubMedCrossRef
63.
64.
65.
Guislain A, Gadiot J, Kaiser A, Jordanova ES, Broeks A, Sanders J, van Boven H, de Gruijl TD, Haanen JB, Bex A, Blank CU (2015) Sunitinib pretreatment improves tumor-infiltrating lymphocyte expansion by reduction in intratumoral content of myeloid-derived suppressor cells in human renal cell carcinoma. Cancer Immunol Immunother 64:1241–1250PubMedCrossRef
66.
Heinrich MC, Blanke CD, Druker BJ, Corless CL (2002) Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20:1692–1703PubMedCrossRef
67.
Hu D, Wang V, Yang M, Abdullah S, Davis DA, Uldrick TS, Polizzotto MN, Veeranna RP, Pittaluga S, Tosato G, Yarchoan R (2015) Induction of Kaposi’s sarcoma-associated herpesvirus-encoded viral interleukin-6 by X-box binding protein 1. J Virol 90:368–378PubMedPubMedCentralCrossRef
68.
Hussein HA, Walker LR, Abdel-Raouf UM, Desouky SA, Montasser AK, Akula SM (2015) Beyond RGD: virus interactions with integrins. Arch Virol 160:2669–2681PubMedCrossRef
69.
Hussein TM, El-Sabaa BM, Hanafy NF (2012) Evaluation of c-kit expression in classic Kaposi’s sarcoma in a cohort of Egyptian patients. J Egypt Natl Canc Inst 24:1–6PubMedCrossRef
70.
Hwang SW, Kim D, Jung JU, Lee HR (2017) KSHV-encoded viral interferon regulatory factor 4 (vIRF4) interacts with IRF7 and inhibits interferon alpha production. Biochem Biophys Res Commun 486:700–705PubMedPubMedCentralCrossRef
71.
Irby RB, Yeatman TJ (2000) Role of Src expression and activation in human cancer. Oncogene 19:5636–5642PubMedCrossRef
72.
73.
Jaraiz-Rodriguez M, Tabernero MD, Gonzalez-Tablas M, Otero A, Orfao A, Medina JM, Tabernero A (2017) A short region of Connexin43 reduces human glioma stem cell migration, invasion, and survival through Src, PTEN, and FAK. Stem cell Reports 9:451–463PubMedPubMedCentralCrossRef
74.
Jensen KK, Manfra DJ, Grisotto MG, Martin AP, Vassileva G, Kelley K, Schwartz TW, Lira SA (2005) The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi’s sarcoma. J Immunol 174:3686–3694PubMedCrossRef
75.
Jones T, Ramos da Silva S, Bedolla R, Ye F, Zhou F, Gao SJ (2014) Viral cyclin promotes KSHV-induced cellular transformation and tumorigenesis by overriding contact inhibition. Cell Cycle 13:845–858PubMedPubMedCentralCrossRef
76.
Just WW, Peranen J (2016) Small GTPases in peroxisome dynamics. Biochim Biophys Acta 1863:1006–1013PubMedCrossRef
77.
Kandemir NO, Gun BD, Bahadir B, Yurdakan G, Ozdemir N, Karadayi N, Ozdamar SO (2010) c-Kit (CD117) expression in classic Kaposi’s sarcoma. Clin Exp Dermatol 35:525–530PubMedCrossRef
78.
Kerr DA, Busarla SVP, Gimbel DC, Sohani AR, Nazarian RM (2017) mTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma. Hum Pathol 65:157–165PubMedCrossRef
79.
Kiss E, Mirzahosseini A, Hubert A, Ambrus A, Orfi L, Horvath P (2017) DNA binding of sunitinib: Spectroscopic evidence via circular dichroism and nuclear magnetic resonance. J Pharm Biomed Anal 150:355–361PubMedCrossRef
80.
Kissel M, Berndt S, Fiebig L, Kling S, Ji Q, Gu Q, Lang T, Hafner FT, Teufel M, Zopf D (2017) Antitumor effects of regorafenib and sorafenib in preclinical models of hepatocellular carcinoma. Oncotarget 8:107096–107108PubMedPubMedCentralCrossRef
81.
Kitada S, Kress CL, Krajewska M, Jia L, Pellecchia M, Reed JC (2008) Bcl-2 antagonist apogossypol (NSC736630) displays single-agent activity in Bcl-2-transgenic mice and has superior efficacy with less toxicity compared with gossypol (NSC19048). Blood 111:3211–3219PubMedPubMedCentralCrossRef
82.
Koon HB, Krown SE, Lee JY, Honda K, Rapisuwon S, Wang Z, Aboulafia D, Reid EG, Rudek MA, Dezube BJ, Noy A (2014) Phase II trial of imatinib in AIDS-associated Kaposi’s sarcoma: AIDS malignancy consortium protocol 042. J Clin Oncol 32:402–408PubMedCrossRef
83.
Krajewska M, Kitada S, Winter JN, Variakojis D, Lichtenstein A, Zhai D, Cuddy M, Huang X, Luciano F, Baker CH, Kim H, Shin E, Kennedy S, Olson AH, Badzio A, Jassem J, Meinhold-Heerlein I, Duffy MJ, Schimmer AD, Tsao M, Brown E, Sawyers A, Andreeff M, Mercola D, Krajewski S, Reed JC (2008) Bcl-B expression in human epithelial and nonepithelial malignancies. Clin Cancer Res 14:3011–3021PubMedPubMedCentralCrossRef
84.
Krygowska AA, Castellano E (2018) PI3K: a crucial piece in the RAS signaling puzzle. Cold Spring Harbor Perspect Med 8:a031450CrossRef
85.
Larkin J, Ascierto PA, Dreno B, Atkinson V, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A (2014) Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371:1867–1876PubMedCrossRef
86.
Lee HR, Doganay S, Chung B, Toth Z, Brulois K, Lee S, Kanketayeva Z, Feng P, Ha T, Jung JU (2014) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4) targets expression of cellular IRF4 and the Myc gene to facilitate lytic replication. J Virol 88:2183–2194PubMedPubMedCentralCrossRef
87.
Lee LA, Resar LM, Dang CV (1995) Cell density and paradoxical transcriptional properties of c-Myc and Max in cultured mouse fibroblasts. J Clin Invest 95:900–904PubMedPubMedCentralCrossRef
88.
Leverson JD, Phillips DC, Mitten MJ, Boghaert ER, Diaz D, Tahir SK, Belmont LD, Nimmer P, Xiao Y, Ma XM, Lowes KN, Kovar P, Chen J, Jin S, Smith M, Xue J, Zhang H, Oleksijew A, Magoc TJ, Vaidya KS, Albert DH, Tarrant JM, La N, Wang L, Tao ZF, Wendt MD, Sampath D, Rosenberg SH, Tse C, Huang DC, Fairbrother WJ, Elmore SW, Souers AJ (2015) Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med 7:279ra240CrossRef
89.
Li M, Lee H, Yoon DW, Albrecht JC, Fleckenstein B, Neipel F, Jung JU (1997) Kaposi’s sarcoma-associated herpesvirus encodes a functional cyclin. J Virol 71:1984–1991PubMedPubMedCentral
90.
Liang D, Hu H, Li S, Dong J, Wang X, Wang Y, He L, He Z, Gao Y, Gao SJ, Lan K (2014) Oncogenic herpesvirus KSHV Hijacks BMP-Smad1-Id signaling to promote tumorigenesis. PLoS Pathog 10:e1004253PubMedPubMedCentralCrossRef
91.
Lugowska I, Kosela-Paterczyk H, Kozak K, Rutkowski P (2015) Trametinib: a MEK inhibitor for management of metastatic melanoma. Onco Targets Ther 8:2251–2259PubMedPubMedCentral
92.
Malaise M, Steinbach D, Corbacioglu S (2009) Clinical implications of c-Kit mutations in acute myelogenous leukemia. Curr Hematol Malig Rep 4:77–82PubMedCrossRef
93.
94.
Martin D, Gutkind JS (2008) Human tumor-associated viruses and new insights into the molecular mechanisms of cancer. Oncogene 27(Suppl 2):S31–S42PubMedCrossRef
95.
Martin D, Galisteo R, Molinolo AA, Wetzker R, Hirsch E, Gutkind JS (2011) PI3Kgamma mediates kaposi’s sarcoma-associated herpesvirus vGPCR-induced sarcomagenesis. Cancer Cell 19:805–813PubMedPubMedCentralCrossRef
96.
McGee JH, Shim SY, Lee SJ, Swanson PK, Jiang Y, Durney MA, Verdine GL (2018) Exceptionally high-affinity Ras binders that remodel its effector domain. J Biol Chem 293:3265–3280PubMedCrossRef
97.
98.
99.
Miles SA, Rezai AR, Salazar-Gonzalez JF, Vander Meyden M, Stevens RH, Logan DM, Mitsuyasu RT, Taga T, Hirano T, Kishimoto T et al (1990) AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci USA 87:4068–4072PubMedCrossRef
100.
101.
Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS (2003) Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23–36PubMedCrossRef
102.
103.
Munshi N, Groopman JE, Gill PS, Ganju RK (2000) c-Src mediates mitogenic signals and associates with cytoskeletal proteins upon vascular endothelial growth factor stimulation in Kaposi’s sarcoma cells. J Immunol 164:1169–1174PubMedCrossRef
104.
Nautiyal J, Majumder P, Patel BB, Lee FY, Majumdar AP (2009) Src inhibitor dasatinib inhibits growth of breast cancer cells by modulating EGFR signaling. Cancer Lett 283:143–151PubMedCrossRef
105.
Pantanowitz L, Schwartz EJ, Dezube BJ, Kohler S, Dorfman RF, Tahan SR (2005) C-Kit (CD117) expression in AIDS-related, classic, and African endemic Kaposi sarcoma. Appl Immunohistochem Mol Morphol 13:162–166PubMedCrossRef
106.
Pozharskaya VP, Weakland LL, Zimring JC, Krug LT, Unger ER, Neisch A, Joshi H, Inoue N, Offermann MK (2004) Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells. J Virol 78:6621–6635PubMedPubMedCentralCrossRef
107.
Prakash O, Tang ZY, Peng X, Coleman R, Gill J, Farr G, Samaniego F (2002) Tumorigenesis and aberrant signaling in transgenic mice expressing the human herpesvirus-8 K1 gene. J Natl Cancer Inst 94:926–935PubMedCrossRef
108.
109.
Purushothaman P, Uppal T, Sarkar R, Verma SC (2016) KSHV-mediated angiogenesis in tumor progression. Viruses 8:E198PubMedCrossRef
110.
Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D (2015) Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372:30–39PubMedCrossRef
111.
Rosean TR, Holman CJ, Tompkins VS, Jing X, Krasowski MD, Rose-John S, Janz S (2016) KSHV-encoded vIL-6 collaborates with deregulated c-Myc to drive plasmablastic neoplasms in mice. Blood Cancer J 6:e398PubMedPubMedCentralCrossRef
112.
Roskoski R Jr (2005) Signaling by kit protein-tyrosine kinase—the stem cell factor receptor. Biochem Biophys Res Commun 337:1–13PubMedCrossRef
113.
Sakakibara S, Tosato G (2011) Viral interleukin-6: role in Kaposi’s sarcoma-associated herpesvirus: associated malignancies. J Interferon Cytokine Res 31:791–801PubMedPubMedCentralCrossRef
114.
Sarid R, Sato T, Bohenzky RA, Russo JJ, Chang Y (1997) Kaposi’s sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat Med 3:293–298PubMedCrossRef
115.
Sarid R, Flore O, Bohenzky RA, Chang Y, Moore PS (1998) Transcription mapping of the Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) genome in a body cavity-based lymphoma cell line (BC-1). J Virol 72:1005–1012PubMedPubMedCentral
116.
Seo T, Lee D, Lee B, Chung JH, Choe J (2000) Viral interferon regulatory factor 1 of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) binds to, and inhibits transactivation of, CREB-binding protein. Biochem Biophys Res Commun 270:23–27PubMedCrossRef
117.
Shin YC, Nakamura H, Liang X, Feng P, Chang H, Kowalik TF, Jung JU (2006) Inhibition of the ATM/p53 signal transduction pathway by Kaposi’s sarcoma-associated herpesvirus interferon regulatory factor 1. J Virol 80:2257–2266PubMedPubMedCentralCrossRef
118.
119.
Soto D, Song C, McLaughlin-Drubin ME (2017) Epigenetic alterations in human papillomavirus-associated cancers. Viruses 9:E248PubMedCrossRef
120.
Suthaus J, Stuhlmann-Laeisz C, Tompkins VS, Rosean TR, Klapper W, Tosato G, Janz S, Scheller J, Rose-John S (2012) HHV-8-encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice. Blood 119:5173–5181PubMedPubMedCentralCrossRef
121.
Swanton C, Mann DJ, Fleckenstein B, Neipel F, Peters G, Jones N (1997) Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins. Nature 390:184–187PubMedCrossRef
122.
Takahashi RH, Choo EF, Ma S, Wong S, Halladay J, Deng Y, Rooney I, Gates M, Hop CE, Khojasteh SC, Dresser MJ, Musib L (2016) Absorption, metabolism, excretion, and the contribution of intestinal metabolism to the oral disposition of [14C] cobimetinib, a MEK inhibitor, in humans. Drug Metab Dispos 44:28–39PubMedCrossRef
123.
Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26:535–584PubMedCrossRef
124.
Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517–521PubMedCrossRef
125.
Trop-Steinberg S, Azar Y (2018) Is Myc an important biomarker? Myc expression in immune disorders and cancer. Am J Med Sci 355:67–75PubMedCrossRef
126.
127.
Veettil MV, Sharma-Walia N, Sadagopan S, Raghu H, Sivakumar R, Naranatt PP, Chandran B (2006) RhoA-GTPase facilitates entry of Kaposi’s sarcoma-associated herpesvirus into adherent target cells in a Src-dependent manner. J Virol 80:11432–11446PubMedPubMedCentralCrossRef
128.
Verschuren EW, Jones N, Evan GI (2004) The cell cycle and how it is steered by Kaposi’s sarcoma-associated herpesvirus cyclin. J Gen Virol 85:1347–1361PubMedCrossRef
129.
Wang F, Guo Y, Li W, Lu C, Yan Q (2017) Generation of a KSHV K13 deletion mutant for vFLIP function study. J Med Virol
130.
Wang L, Dittmer DP, Tomlinson CC, Fakhari FD, Damania B (2006) Immortalization of primary endothelial cells by the K1 protein of Kaposi’s sarcoma-associated herpesvirus. Cancer Res 66:3658–3666PubMedCrossRef
131.
Wang X, He Z, Xia T, Li X, Liang D, Lin X, Wen H, Lan K (2014) Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1. Cancer Res 74:2026–2037PubMedCrossRef
132.
133.
Widmer I, Wernli M, Bachmann F, Gudat F, Cathomas G, Erb P (2002) Differential expression of viral Bcl-2 encoded by Kaposi’s sarcoma-associated herpesvirus and human Bcl-2 in primary effusion lymphoma cells and Kaposi’s sarcoma lesions. J Virol 76:2551–2556PubMedPubMedCentralCrossRef
134.
Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109PubMedCrossRef
135.
Wu H, Liu L, Xiao J, Chi M, Qu Y, Feng H (2015) Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. Viruses 7:1627–1641PubMedPubMedCentralCrossRef
136.
Xiao B, Verma SC, Cai Q, Kaul R, Lu J, Saha A, Robertson ES (2010) Bub1 and CENP-F can contribute to Kaposi’s sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. J Virol 84:9718–9732PubMedPubMedCentralCrossRef
137.
Xu L, Xie Q, Qi L, Wang C, Xu N, Liu W, Yu Y, Li S, Xu Y (2018) Bcl-2 overexpression reduces cisplatin cytotoxicity by decreasing ER-mitochondrial Ca2+ signaling in SKOV3 cells. Oncol Rep 39:985–992PubMed
138.
Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A (1987) Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. Embo J 6:3341–3351PubMedPubMedCentralCrossRef
139.
Ye FC, Zhou FC, Yoo SM, Xie JP, Browning PJ, Gao SJ (2004) Disruption of Kaposi’s sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence. J Virol 78:11121–11129PubMedPubMedCentralCrossRef
140.
141.
142.
Yoo SM, Zhou FC, Ye FC, Pan HY, Gao SJ (2005) Early and sustained expression of latent and host modulating genes in coordinated transcriptional program of KSHV productive primary infection of human primary endothelial cells. Virology 343:47–64PubMedPubMedCentralCrossRef
143.
Yoshida N, Doisaki S, Kojima S (2012) Current management of juvenile myelomonocytic leukemia and the impact of RAS mutations. Paediatr Drugs 14:157–163PubMedCrossRef
144.
Yu F, Harada JN, Brown HJ, Deng H, Song MJ, Wu TT, Kato-Stankiewicz J, Nelson CG, Vieira J, Tamanoi F, Chanda SK, Sun R (2007) Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus. PLoS Pathog 3:e44PubMedPubMedCentralCrossRef
145.
Zachos G, Spandidos DA (1998) Transcriptional regulation of the c-H-ras1 gene by the P53 protein is implicated in the development of human endometrial and ovarian tumours. Oncogene 16:3013–3017PubMedCrossRef
146.
Zhang E, Cotton VE, Hidalgo-Bravo A, Huang Y, Bell AJ, Jarrett RF, Wilkie GS, Davison AJ, Nacheva EP, Siebert R, Majid A, Kelpanides I, Jayne S, Dyer MJ, Royle NJ (2016) HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus-6A from the telomere of chromosome 19q. Sci Rep 6:22730PubMedPubMedCentralCrossRef
147.
Zhang P, Kawakami H, Liu W, Zeng X, Strebhardt K, Tao K, Huang S, Sinicrope FA (2017) Targeting CDK1 and MEK/ERK overcomes apoptotic resistance in BRAF mutated human colorectal cancer. Mol Cancer Res
148.
149.
Zhi H, Zahoor MA, Shudofsky AM, Giam CZ (2015) KSHV vCyclin counters the senescence/G1 arrest response triggered by NF-kappaB hyperactivation. Oncogene 34:496–505PubMedCrossRef
150.
Zhong W, Wang H, Herndier B, Ganem D (1996) Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. Proc Natl Acad Sci USA 93:6641–6646PubMedCrossRef
151.
Zhu X, Guo Y, Yao S, Yan Q, Xue M, Hao T, Zhou F, Zhu J, Qin D, Lu C (2014) Synergy between Kaposi’s sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway. Oncogene 33:1986–1996PubMedCrossRef
Metadata
Title
Cellular and viral oncogenes: the key to unlocking unknowns of Kaposi’s sarcoma-associated herpesvirus pathogenesis
Authors
Hosni A. M. Hussein
Ikenna B. Okafor
Lia R. Walker
Usama M. Abdel-Raouf
Shaw M. Akula
Publication date
01-10-2018
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 10/2018
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-018-3918-3

Other articles of this Issue 10/2018

Archives of Virology 10/2018 Go to the issue

Brief Report

Development of a TaqMan probe-based quantitative reverse transcription PCR assay for detection of Getah virus RNA

Original Article

Hepatitis C virus serologic relapse after treatment with direct-acting antivirals is dependent on viral RNA levels in peripheral blood mononuclear cells and the grade of liver cirrhosis

Brief Report

First evidence of the presence of adenovirus type 8 in myocardium of patients with severe idiopathic dilated cardiomyopathy

Original Article

Biological characterization of wild-bird-origin avian avulavirus 1 and efficacy of currently applied vaccines against potential infection in commercial poultry

Brief Report

Getah virus epizootic among wild boars in Japan around 2012

Brief Report

Genome polarity of RNA viruses reflects the different evolutionary pressures shaping codon usage
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits