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E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection

DOI: 10.1371/journal.ppat.1005415

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Abstract:

Interferons (IFNs) are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad) replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC) and TERT-immortalized normal human diploid fibroblasts (HDF-TERT). IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib), a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

 References

[1]  Hoffmann HH, Schneider WM, Rice CM (2015) Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol 36: 124–138. doi: 10.1016/j.it.2015.01.004. pmid:25704559
[2]  McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A (2015) Type I interferons in infectious disease. Nat Rev Immunol 15: 87–103. doi: 10.1038/nri3787. pmid:25614319
[3]  Samarajiwa SA, Forster S, Auchettl K, Hertzog PJ (2009) INTERFEROME: the database of interferon regulated genes. Nucleic Acids Res 37: D852–857. doi: 10.1093/nar/gkn732. pmid:18996892
[4]  Echavarria M (2008) Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 21: 704–715. doi: 10.1128/CMR.00052-07. pmid:18854488
[5]  Anderson KP, Fennie EH (1987) Adenovirus early region 1A modulation of interferon antiviral activity. J Virol 61: 787–795. pmid:3027405
[6]  Kitajewski J, Schneider RJ, Safer B, Munemitsu SM, Samuel CE, et al. (1986) Adenovirus VAI RNA antagonizes the antiviral action of interferon by preventing activation of the interferon-induced eIF-2 alpha kinase. Cell 45: 195–200. pmid:3698097 doi: 10.1016/0092-8674(86)90383-1
[7]  Ullman AJ, Reich NC, Hearing P (2007) Adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral response. J Virol 81: 4744–4752. pmid:17301128 doi: 10.1128/jvi.02385-06
[8]  Hendrickx R, Stichling N, Koelen J, Kuryk L, Lipiec A, et al. (2014) Innate immunity to adenovirus. Hum Gene Ther 25: 265–284. doi: 10.1089/hum.2014.001. pmid:24512150
[9]  Fonseca GJ, Cohen MJ, Nichols AC, Barrett JW, Mymryk JS (2013) Viral retasking of hBre1/RNF20 to recruit hPaf1 for transcriptional activation. PLoS Pathog 9: e1003411. doi: 10.1371/journal.ppat.1003411. pmid:23785282
[10]  Fonseca GJ, Thillainadesan G, Yousef AF, Ablack JN, Mossman KL, et al. (2012) Adenovirus evasion of interferon-mediated innate immunity by direct antagonism of a cellular histone posttranslational modification. Cell Host Microbe 11: 597–606. doi: 10.1016/j.chom.2012.05.005. pmid:22704620
[11]  Chahal JS, Gallagher C, DeHart CJ, Flint SJ (2013) The repression domain of the E1B 55-kilodalton protein participates in countering interferon-induced inhibition of adenovirus replication. J Virol 87: 4432–4444. doi: 10.1128/JVI.03387-12. pmid:23388716
[12]  Chahal JS, Qi J, Flint SJ (2012) The human adenovirus type 5 E1B 55 kDa protein obstructs inhibition of viral replication by type I interferon in normal human cells. PLoS Pathogens 8: e1002853. doi: 10.1371/journal.ppat.1002853. pmid:22912576
[13]  Geoffroy MC, Chelbi-Alix MK (2011) Role of promyelocytic leukemia protein in host antiviral defense. J Interferon Cytokine Res 31: 145–158. doi: 10.1089/jir.2010.0111. pmid:21198351
[14]  Ullman AJ, Hearing P (2008) Cellular proteins PML and Daxx mediate an innate antiviral defense antagonized by the adenovirus E4 ORF3 protein. J Virol 82: 7325–7335. doi: 10.1128/JVI.00723-08. pmid:18480450
[15]  Schreiner S, Wimmer P, Sirma H, Everett RD, Blanchette P, et al. (2010) Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in human adenovirus-infected cells. J Virol 84: 7029–7038. doi: 10.1128/JVI.00074-10. pmid:20484509
[16]  Toth K, Lee SR, Ying B, Spencer JF, Tollefson AE, et al. (2015) STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control. PLoS Pathog 11: e1005084. doi: 10.1371/journal.ppat.1005084. pmid:26291525
[17]  Berk AJ (2005) Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Oncogene 24: 7673–7685. pmid:16299528 doi: 10.1038/sj.onc.1209040
[18]  Bruder JT, Hearing P (1989) Nuclear factor EF-1A binds to the adenovirus E1A core enhancer element and to other transcriptional control regions. Mol Cell Biol 9: 5143–5153. pmid:2601713 doi: 10.1128/mcb.9.11.5143
[19]  Bruder JT, Hearing P (1991) Cooperative binding of EF-1A to the E1A enhancer region mediates synergistic effects on E1A transcription during adenovirus infection. J Virol 65: 5084–5087. pmid:1651424
[20]  Hearing P, Shenk T (1983) The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Cell 33: 695–703. pmid:6871991 doi: 10.1016/0092-8674(83)90012-0
[21]  Hearing P, Shenk T (1986) The adenovirus type 5 E1A enhancer contains two functionally distinct domains: one is specific for E1A and the other modulates all early units in cis. Cell 33: 695–703. doi: 10.1016/0092-8674(86)90387-9
[22]  LaMarco K, Thompson CC, Byers BP, Walton EM, McKnight SL (1991) Identification of Ets- and notch-related subunits in GA binding protein. Science 253: 789–792. pmid:1876836 doi: 10.1126/science.1876836
[23]  Thompson CC, Brown TA, McKnight SL (1991) Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex. Science 253: 762–768. pmid:1876833 doi: 10.1126/science.1876833
[24]  Chen J, Morral N, Engel DA (2007) Transcription releases protein VII from adenovirus chromatin. Virol 369: 411–422. doi: 10.1016/j.virol.2007.08.012
[25]  Freimuth PI, Ginsberg HS (1986) Codon insertion mutants of the adenovirus terminal protein. Proc Natl Acad Sci USA 83: 7816–7820. pmid:3020558 doi: 10.1073/pnas.83.20.7816
[26]  Miralles VJ, Cortes P, Stone N, Reinberg D (1989) The adenovirus inverted terminal repeat functions as an enhancer in a cell-free system. J Biol Chem 264: 10763–10772. pmid:2525131
[27]  Gr？ble M, Hearing P (1990) Adenovirus type 5 packaging domain is composed of a repeated element that is functionally redundant. J Virol 64: 2047–2056. pmid:2325200
[28]  Kovesdi I, Reichel R, Nevins JR (1987) Role of an adenovirus E2 promoter binding factor in E1A-mediated coordinate gene control. Proc Natl Academy Sci USA 84: 2180–2184. doi: 10.1073/pnas.84.8.2180
[29]  Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57–70. pmid:10647931 doi: 10.1016/s0092-8674(00)81683-9
[30]  Dickson MA (2014) Molecular pathways: CDK4 inhibitors for cancer therapy. Clin Cancer Res 20: 3379–3383. doi: 10.1158/1078-0432.CCR-13-1551. pmid:24795392
[31]  Mallette FA, Goumard S, Gaumont-Leclerc M-F, Moiseeva O, Ferbeyre G (2004) Human fibroblasts require the Rb family of tumor suppressors, but not p53, for PML-induced senescence. Oncogene 23: 91–99. pmid:14712214 doi: 10.1038/sj.onc.1206886
[32]  Vernier M, Bourdeau V, Gaumont-Leclerc M-F, Moiseeva O, Bégin V, et al. (2011) Regulation of E2Fs and senescence by PML nuclear bodies. Genes Devel 25: 41–50. doi: 10.1101/gad.1975111. pmid:21205865
[33]  Vernier M, Ferbeyre G (2014) Complete senescence: RB and PML share the task. Cell Cycle 13: 696. doi: 10.4161/cc.28090. pmid:24526117
[34]  Glass M, Everett RD (2012) Components of PML Nuclear Bodies (ND10) act cooperatively to repress herpesvirus infection. J Virol 87: 2174–2185. doi: 10.1128/JVI.02950-12. pmid:23221561
[35]  Diner BA, Lum KK, Cristea IM (2015) The Emerging Role of Nuclear Viral DNA Sensors. J Biol Chem 290: 26412–26421. doi: 10.1074/jbc.R115.652289. pmid:26354430
[36]  Kwak JC, Ongusaha PP, Ouchi T, Lee SW (2003) IFI16 as a negative regulator in the regulation of p53 and p21(Waf1). J Biol Chem 278: 40899–40904. pmid:12925527 doi: 10.1074/jbc.m308012200
[37]  Xin H, Curry J, Johnstone RW, Nickoloff BJ, Choubey D (2003) Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence. Oncogene 22: 4831–4840. pmid:12894224 doi: 10.1038/sj.onc.1206754
[38]  Hertel L, Rolle S, De Andrea M, Azzimonti B, Osello R, et al. (2000) The retinoblastoma protein is an essential mediator that links the interferon-inducible 204 gene to cell-cycle regulation. Oncogene 19: 3598–3608. pmid:10951565 doi: 10.1038/sj.onc.1203697
[39]  Garnett CT, Erdman D, Xu W, Gooding LR (2002) Prevalence and quantitation of species C adenovirus DNA in human mucosal lymphocytes. J Virol 76: 10608–10616. pmid:12368303 doi: 10.1128/jvi.76.21.10608-10616.2002
[40]  Garnett CT, Talekar G, Mahr JA, Huang W, Zhang Y, et al. (2009) Latent species C adenoviruses in human tonsil tissues. J Virol 83: 2417–2428. doi: 10.1128/JVI.02392-08. pmid:19109384
[41]  Zhang Y, Huang W, Ornelles DA, Gooding LR (2010) Modeling adenovirus latency in human lymphocyte cell lines. J Virol 84: 8799–8810. doi: 10.1128/JVI.00562-10. pmid:20573817
[42]  Harbour JW, Dean DC (2000) The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev 14: 2393–2409. pmid:11018009 doi: 10.1101/gad.813200
[43]  Fox JP, Brandt CD, Wassermann FE, Hall CE, Spigland I, et al. (1969) The virus watch program: a continuing surveillance of viral infections in metropolitan New York families. VI. Observations of adenovirus infections: virus excretion patterns, antibody response, efficiency of surveillance, patterns of infections, and relation to illness. Am J Epidemiol 89: 25–50. pmid:4303049
[44]  Fox JP, Hall CE, Cooney MK (1977) The Seattle Virus Watch. VII. Observations of adenovirus infections. Am J Epidemiol 105: 362–386. pmid:192073
[45]  Horvath J, Palkonyay L, Weber J (1986) Group C adenovirus DNA sequences in human lymohoid cells. J Virol 59: 189–192. pmid:3486983
[46]  Proen？a-Módena JL, Buzatto GP, Paula FE, Saturno TH, Delcaro LS, et al. (2014) Respiratory viruses are continuously detected in children with chronic tonsillitis throughout the year. Int J Pediatr Otorhinolaryngol 78: 1655–1661. doi: 10.1016/j.ijporl.2014.07.015. pmid:25128448
[47]  Roy S, Calcedo R, Medina-Jaszek A, Keough M, Peng H, et al. (2011) Adenoviruses in lymphocytes of the human gastro-intestinal tract. PLoS One 6: e24859. doi: 10.1371/journal.pone.0024859. pmid:21980361
[48]  Kovesdi I, Reichel R, Nevins JR (1986) Identification of a cellular transcription factor involved in E1A trans-activation. Cell 45: 219–228. pmid:2938741 doi: 10.1016/0092-8674(86)90386-7
[49]  Boutell C, Everett RD (2013) Regulation of alphaherpesvirus infections by the ICP0 family of proteins. J Gen Virol 94: 465–481. doi: 10.1099/vir.0.048900-0. pmid:23239572
[50]  Tavalai N, Stamminger T (2011) Intrinsic cellular defense mechanisms targeting human cytomegalovirus. Virus Res 157: 128–133. doi: 10.1016/j.virusres.2010.10.002. pmid:20934469
[51]  Giberson AN, Davidson AR, Parks RJ (2012) Chromatin structure of adenovirus DNA throughout infection. Nucl Acids Res 40: 2369–2376. doi: 10.1093/nar/gkr1076. pmid:22116065
[52]  Karen KA, Hearing P (2011) Adenovirus core protein VII protects the viral genome from a DNA damage response at early times after infection. J Virol 85: 4135–4142. doi: 10.1128/JVI.02540-10. pmid:21345950
[53]  Choubey D, Gutterman JU (1997) Inhibition of E2F-4/DP-1-stimulated transcription by p202. Oncogene 15: 291–301. pmid:9233764 doi: 10.1038/sj.onc.1201184
[54]  Choubey D, Li SJ, Datta B, Gutterman JU, Lengyel P (1996) Inhibition of E2F-mediated transcription by p202. EMBO J 15: 5668–5678. pmid:8896460
[55]  Look DC, Roswit WT, Frick AG, Gris-Alevy Y, Dickhaus DM, et al. (1998) Direct suppression of Stat1 function during adenoviral infection. Immunity 9: 871–880. pmid:9881977 doi: 10.1016/s1074-7613(00)80652-4
[56]  Yu J, Boyapati A, Rundell K (2001) Critical role for SV40 small-t antigen in human cell transformation. Virol 290: 192–198. doi: 10.1006/viro.2001.1204
[57]  Schaack J, Guo X, Ho WY, Karlok M, Chen C, et al. (1995) Adenovirus type 5 precursor terminal protein-expressing 293 and HeLa cell lines. J Virol 69: 4079–4085. pmid:7769665
[58]  Jones N, Shenk T (1979) Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell 17: 683–689. pmid:476833 doi: 10.1016/0092-8674(79)90275-7
[59]  Chartier C, Degryse E, Gantzer M, Dieterle A, Pavirani A, et al. (1996) Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli. J Virol 70: 4805–4810. pmid:8676512
[60]  Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucl Acids Res 29: e45. pmid:11328886 doi: 10.1093/nar/29.9.e45
[61]  Zheng Y, Hearing P (2014) The use of chromatin immunoprecipitation (ChIP) to study the binding of viral proteins to the adenovirus genome in vivo. Methods Molec Biol 1089: 79–87. doi: 10.1007/978-1-62703-679-5_6

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