Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Beyond Viral Interferon Regulatory Factors: Immune Evasion Strategies

  • Myoung, Jinjong (Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material Science, College of Natural Science, Jeonbuk National University) ;
  • Lee, Shin-Ae (Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California) ;
  • Lee, Hye-Ra (Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University)
  • Received : 2019.10.08
  • Accepted : 2019.10.24
  • Published : 2019.12.28
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Abstract

The innate immune response serves as a first-line-of-defense mechanism for a host against viral infection. Viruses must therefore subvert this anti-viral response in order to establish an efficient life cycle. In line with this fact, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes numerous genes that function as immunomodulatory proteins to antagonize the host immune system. One such mechanism through which KSHV evades the host immunity is by encoding a viral homolog of cellular interferon (IFN) regulatory factors (IRFs), known as vIRFs. Herein, we summarize recent advances in the study of the immunomodulatory strategies of KSHV vIRFs and their effects on KSHV-associated pathogenesis.

Keywords

References

  1. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, et al. 1995. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86: 1276-1280. https://doi.org/10.1182/blood.v86.4.1276.bloodjournal8641276
  2. Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, et al. 1996. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 88: 645-656. https://doi.org/10.1182/blood.v88.2.645.bloodjournal882645
  3. Ganem D. 2010. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J. Clin. Invest. 120: 939-949. https://doi.org/10.1172/JCI40567
  4. Lee HR, Amatya R, Jung JU. 2015. Multi-step regulation of innate immune signaling by Kaposi's sarcoma-associated herpesvirus. Virus Res. 209: 39-44. https://doi.org/10.1016/j.virusres.2015.03.004
  5. Li M, Lee H, Guo J, Neipel F, Fleckenstein B, Ozato K, et al. 1998. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor. J. Virol. 72: 5433-40. https://doi.org/10.1128/jvi.72.7.5433-5440.1998
  6. Burysek L, Yeow WS, Lubyova B, Kellum M, Schafer SL, Huang YQ, et al. 1999. Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J. Virol. 73: 7334-42. https://doi.org/10.1128/jvi.73.9.7334-7342.1999
  7. Li M, Damania B, Alvarez X, Ogryzko V, Ozato K, Jung JU. 2000. Inhibition of p300 histone acetyltransferase by viral interferon regulatory factor. Mol. Cell Biol. 20: 8254-8263. https://doi.org/10.1128/MCB.20.21.8254-8263.2000
  8. Jacobs SR, Gregory SM, West JA, Wollish AC, Bennett CL, Blackbourn DJ, et al. 2013. The viral interferon regulatory factors of kaposi's sarcoma-associated herpesvirus differ in their inhibition of interferon activation mediated by toll-like receptor 3. J. Virol. 87: 798-806. https://doi.org/10.1128/JVI.01851-12
  9. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, et al. 2015. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520: 553-557. https://doi.org/10.1038/nature14156
  10. Ma Z, Jacobs SR, West JA, Stopford C, Zhang Z, Davis Z, et al. 2015. Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc. Natl. Acad. Sci. USA 112: E4306-15. https://doi.org/10.1073/pnas.1503831112
  11. Jenner RG, Alba MM, Boshoff C, Kellam P. 2001. Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J. Virol. 75: 891-902. https://doi.org/10.1128/JVI.75.2.891-902.2001
  12. Fuld S, Cunningham C, Klucher K, Davison AJ, Blackbourn DJ. 2006. Inhibition of interferon signaling by the Kaposi's sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein. J. Virol. 80: 3092-3097. https://doi.org/10.1128/JVI.80.6.3092-3097.2006
  13. Burysek L, Yeow WS, Pitha PM. 1999. Unique properties of a second human herpesvirus 8 -encoded interferon regulatory factor (vIRF-2). J. Hum. Virol. 2: 19-32.
  14. Areste C, Mutocheluh M, Blackbourn DJ. 2009. Identification of caspase-mediated decay of interferon regulatory factor-3, exploited by a Kaposi sarcoma-associated herpesvirus immunoregulatory protein. J. Biol. Chem. 284: 23272-23285. https://doi.org/10.1074/jbc.M109.033290
  15. Burysek L, Pitha PM. 2001. Latently expressed human herpesvirus 8-encoded interferon regulatory factor 2 inhibits double-stranded RNA-activated protein kinase. J. Virol. 75: 2345-2352. https://doi.org/10.1128/JVI.75.5.2345-2352.2001
  16. Lubyova B, Kellum MJ, Frisancho AJ, Pitha PM. 2004. Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7. J. Biol. Chem. 279: 7643-7654. https://doi.org/10.1074/jbc.M309485200
  17. Lubyova B, Pitha PM. 2000. Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors. J. Virol. 74: 8194-8201. https://doi.org/10.1128/JVI.74.17.8194-8201.2000
  18. Joo CH, Shin YC, Gack M, Wu L, Levy D, Jung JU. 2007. Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi's sarcomaassociated herpesvirus viral IRF homolog vIRF3. J. Virol. 81: 8282-8292. https://doi.org/10.1128/JVI.00235-07
  19. Wies E, Hahn AS, Schmidt K, Viebahn C, Rohland N, Lux A, et al. 2009. The Kaposi's Sarcoma-associated Herpesvirusencoded vIRF-3 inhibits cellular IRF-5. J. Biol. Chem. 284: 8525-8538. https://doi.org/10.1074/jbc.M809252200
  20. 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: 700-705. https://doi.org/10.1016/j.bbrc.2017.03.101
  21. Green DR, Llambi F. 2005. Cell Death Signaling. Cold Spring Harb Perspect. Biol. 7(12).
  22. Willis SN, Adams JM. 2005. Life in the balance: how BH3-only proteins induce apoptosis. Curr. Opin. Cell Biol. 17: 617-625. https://doi.org/10.1016/j.ceb.2005.10.001
  23. Kirchhoff S, Sebens T, Baumann S, Krueger A, Zawatzky R, Li-Weber M, et al. 2002. Viral IFN-regulatory factors inhibit activation-induced cell death via two positive regulatory IFN-regulatory factor 1-dependent domains in the CD95 ligand promoter. J. Immunol. 168: 1226-1234. https://doi.org/10.4049/jimmunol.168.3.1226
  24. Peter ME, Hellbardt S, Schwartz-Albiez R, Westendorp MO, Walczak H, Moldenhauer G, et al. 1995. Cell surface sialylation plays a role in modulating sensitivity towards APO-1-mediated apoptotic cell death. Cell Death Differ. 2: 163-171.
  25. Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A, et al. 2015. The role of CD95 and CD95 ligand in cancer. Cell Death Differ. 22: 549-559. https://doi.org/10.1038/cdd.2015.3
  26. Fulda S, Debatin KM. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25: 4798-4811. https://doi.org/10.1038/sj.onc.1209608
  27. Kim Y, Cha S, Seo T. 2016. Activation of the phosphatidylinositol 3-kinase/Akt pathway by viral interferon regulatory factor 2 of Kaposi's sarcoma-associated herpesvirus. Biochem. Biophys. Res. Commun. 470: 650-656. https://doi.org/10.1016/j.bbrc.2016.01.087
  28. Choi YB, Sandford G, Nicholas J. 2012. Human herpesvirus 8 interferon regulatory factor-mediated BH3-only protein inhibition via Bid BH3-B mimicry. PLoS Pathog. 8: e1002748. https://doi.org/10.1371/journal.ppat.1002748
  29. Hwang KY, Choi YB. 2016. Modulation of mitochondrial antiviral signaling by human herpesvirus 8 interferon regulatory factor 1. J. Virol. 90: 506-520. https://doi.org/10.1128/JVI.01903-15
  30. Vogelstein B, Lane D, Levine AJ. 2000. Surfing the p53 network. Nature 408: 307-310. https://doi.org/10.1038/35042675
  31. Lee HR, Kim MH, Lee JS, Liang C, Jung JU. 2009. Viral interferon regulatory factors. J. Interferon Cytokine Res. 29: 621-627. https://doi.org/10.1089/jir.2009.0067
  32. Wang S, Zhao Y, Aguilar A, Bernard D, Yang CY. 2017. Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapy: Progress and Challenges. Cold Spring Harb Perspect Med. 7(5). pii: a026245..
  33. Vazquez A, Bond EE, Levine AJ, Bond GL. 2008. The genetics of the p53 pathway, apoptosis and cancer therapy. Nat. Rev. Drug Discov. 7: 979-987. https://doi.org/10.1038/nrd2656
  34. Shin YC, Nakamura H, Liang X, Feng P, Chang H, Kowalik TF, et al. 2006. Inhibition of the ATM/p53 signal transduction pathway by Kaposi's sarcoma-associated herpesvirus interferon regulatory factor 1. J. Virol. 80: 2257-2266. https://doi.org/10.1128/JVI.80.5.2257-2266.2006
  35. Seo T, Park J, Lee D, Hwang SG, Choe J. 2001.Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus binds to p53 and represses p53-dependent transcription and apoptosis. J. Virol. 75: 6193-6198. https://doi.org/10.1128/JVI.75.13.6193-6198.2001
  36. Chavoshi S, Egorova O, Lacdao IK, Farhadi S, Sheng Y, Saridakis V. 2016. Identification of Kaposi Sarcoma Herpesvirus (KSHV) vIRF1 protein as a novel interaction partner of human Deubiquitinase USP7. J. Biol. Chem. 291: 6281-6291. https://doi.org/10.1074/jbc.M115.710632
  37. Lee HR, Toth Z, Shin YC, Lee JS, Chang H, Gu W, et al. 2009. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 targets MDM2 to deregulate the p53 tumor suppressor pathway. J. Virol. 83: 6739-6747. https://doi.org/10.1128/JVI.02353-08
  38. Lee HR, Choi WC, Lee S, Hwang J, Hwang E, Guchhait K, et al. 2011. Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. Nat. Struct. Mol. Biol. 18: 1336-1344. https://doi.org/10.1038/nsmb.2142
  39. Pantry SN, Medveczky PG. 2009. Epigenetic regulation of Kaposi's sarcoma-associated herpesvirus replication. Semin. Cancer Biol. 19: 153-157. https://doi.org/10.1016/j.semcancer.2009.02.010
  40. 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: 9398-9410. https://doi.org/10.1128/JVI.03315-12
  41. Takaoka A, Tamura T, Taniguchi T. 2008. Interferon regulatory factor family of transcription factors and regulation of oncogenesis. Cancer Sci. 99: 467-478. https://doi.org/10.1111/j.1349-7006.2007.00720.x
  42. Park J, Lee MS, Yoo SM, Jeong KW, Lee D, Choe J, et al. 2007. Identification of the DNA sequence interacting with Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 1. J. Virol. 81: 12680-12684. https://doi.org/10.1128/JVI.00556-07
  43. Hew K, Dahlroth SL, Venkatachalam R, Nasertorabi F, Lim BT, Cornvik T, et al. 2013. The crystal structure of the DNAbinding domain of vIRF-1 from the oncogenic KSHV reveals a conserved fold for DNA binding and reinforces its role as a transcription factor. Nucleic Acids Res. 41: 4295-4306. https://doi.org/10.1093/nar/gkt082
  44. Seo T, Park J, Choe J. 2005. Kaposi's sarcoma-associated herpesvirus viral IFN regulatory factor 1 inhibits transforming growth factor-beta signaling. Cancer Res. 65: 1738-1747. https://doi.org/10.1158/0008-5472.CAN-04-2374
  45. Hu H, Dong J, Liang D, Gao Z, Bai L, Sun R, et al. 2016. Genome-wide mapping of the binding sites and structural analysis of Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 2 reveal that it is a DNAbinding transcription factor. J. Virol. 290: 1158-1168.
  46. Koch S, Damas M, Freise A, Hage E, Dhingra A, Ruckert J, et al. 20019. Kaposi's sarcoma-associated herpesvirus vIRF2 protein utilizes an IFN-dependent pathway to regulate viral early gene expression. PLoS Pathog. 15: e1007743. https://doi.org/10.1371/journal.ppat.1007743
  47. Lee HR, Li F, Choi UY, Yu HR, Aldrovandi GM, Feng P, et al. 2018. Deregulation of HDAC5 by viral interferon regulatory factor 3 plays an essential role in Kaposi's sarcomaassociated herpesvirus-induced lymphangiogenesis. Mbio 9(1). pii: e02217-17
  48. Rivas C, Thlick AE, Parravicini C, Moore PS, Chang Y. 2001. Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cellspecific latent viral protein that inhibits p53. J. Virol. 75: 429-438. https://doi.org/10.1128/JVI.75.1.429-438.2001
  49. Xi X, Persson LM, O'Brien MW, Mohr I, Wilson AC. 2012. Cooperation between viral interferon regulatory factor 4 and RTA to activate a subset of Kaposi's sarcoma-associated herpesvirus lytic promoters. J. Virol. 86: 1021-1033. https://doi.org/10.1128/JVI.00694-11
  50. Lee HR, Doganay S, Chung B, Toth Z, Brulois K, Lee S, et al. 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: 2183-2194. https://doi.org/10.1128/JVI.02106-13
  51. Yu HR, Kim YJ, Lee HR. 2018. KSHV vIRF4 enhances BCL6 transcription via downregulation of IRF4 expression. Biochem. Biophys. Res. Commun. 496: 1128-1133. https://doi.org/10.1016/j.bbrc.2018.01.154
  52. Shaffer A L, Emre NC, Romesser PB, Staudt LM. IRF4: Immunity. Malignancy! Therapy? Clin. Cancer Res. 15: 2954- 2961. https://doi.org/10.1158/1078-0432.CCR-08-1845
  53. Lee HR, Mitra J , Lee S, Gao SJ, Oh TK, Kim MH, et al. 2016. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4) perturbs the G1-S cell cycle progression via deregulation of the cyclin D1 gene. J. Virol. 90: 1139-1143. https://doi.org/10.1128/JVI.01897-15
  54. Robinson BA, Estep RD, Messaoudi I, Rogers KS, Wong SW. 2012. Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection. J. Virol. 86: 2197-2211. https://doi.org/10.1128/JVI.05047-11
  55. Springgay LK, Fitzpatrick K, Park B, Estep RD, Wong SW. 2019. Rhesus macaque rhadinovirus encodes a viral interferon regulatory factor to disrupt promyelocytic leukemia nuclear bodies and antagonize type I interferon signaling. J. Virol. 93(6). pii: e02147-18.

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