Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence

PLoS Pathogens

Volumn 12, Issue 3, 2016, Pages

  Kolb, Aaron W ^a   Lee, Kyubin ^a,b   Larsen, Inna ^a   Craven, Mark ^a,b   Brandt, Curtis R ^a  

^a UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^b University of Wisconsin   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONCEPTUAL FRAMEWORK; CONTROLLED STUDY; EYE INFECTION; FEMALE; GENETIC POLYMORPHISM; GENOME ANALYSIS; GENOTYPE PHENOTYPE CORRELATION; HERPES SIMPLEX VIRUS 1; IMMUNOMODULATION; INNATE IMMUNITY; LINEAR REGRESSION ANALYSIS; MONTE CARLO METHOD; MORTALITY; MOUSE; NONHUMAN; PROTEIN INTERACTION; QUANTITATIVE TRAIT LOCUS MAPPING; SCORING SYSTEM; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS; VIRUS REPLICATION; VIRUS VIRULENCE; ANIMAL; CHLOROCEBUS AETHIOPS; DNA SEQUENCE; GENETIC ASSOCIATION STUDY; GENETICS; IMMUNOLOGY; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; PATHOGENICITY; QUANTITATIVE TRAIT LOCUS; STATISTICAL MODEL; VERO CELL LINE; VIROLOGY; VIRULENCE;

VIRULENCE FACTOR; VIRUS DNA;

ANIMALS; BASE SEQUENCE; CERCOPITHECUS AETHIOPS; DNA, VIRAL; EYE INFECTIONS; GENETIC ASSOCIATION STUDIES; HERPESVIRUS 1, HUMAN; LINEAR MODELS; MICE; MOLECULAR SEQUENCE DATA; QUANTITATIVE TRAIT LOCI; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS, DNA; VERO CELLS; VIRULENCE; VIRULENCE FACTORS; VIRUS REPLICATION;

EID: 84962467054     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005499     Document Type: Article

References (74)

1. Whitley RJ, Roizman B, Knipe D, Whitley RJ, Herpes simplex viruses. In: Fields Virology. Philadelphia: Lippincott-Raven; 2006. p. 2501–601.
2. Kortekangas-Savolainen O, Orhanen E, Puodinketo T, Vuorinen T, Epidemiology of genital herpes simplex virus type 1 and 2 infections in southwestern Finland during a 10-year period (2003–2012). Sex Transm Dis. 2014;41(4):268–71. Epub 2014/03/14. doi: 10.1097/OLQ.0000000000000101 00007435-201404000-00010 [pii]. 24622640.
3. Pena KC, Adelson ME, Mordechai E, Blaho JA, Genital herpes simplex virus type 1 in women: detection in cervicovaginal specimens from gynecological practices in the United States. J Clin Microbiol. 2010;48(1):150–3. Epub 2009/11/20. doi: 10.1128/JCM.01336-09 JCM.01336-09 [pii]. 19923487; PubMed Central PMCID: PMC2812291.
4. Liesegang TJ, Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1–13. 11188989.
5. Feenstra RP, Tseng SC, Comparison of fluorescein and rose bengal staining. Ophthalmology. 1992;99:605–17. 1374875
6. Brandt CR, Virulence genes in herpes simplex virus type 1 corneal infection. Curr Eye Res. 2004;29(2–3):103–17. Epub 2004/10/30. doi: 6YLCMXTKU9KN1DXC [pii] doi: 10.1080/0271368049050453315512957.
7. Brandt CR, The role of viral and host genes in corneal infection with herpes simplex virus type 1. Exp Eye Res. 2005;80(5):607–21. Epub 2005/05/03. doi: S0014-4835(04)00269-6 [pii] doi: 10.1016/j.exer.2004.09.00715862167.
8. Doymaz MZ, Rouse BT, Immunopathology of herpes simplex virus infections. Curr Top Microbiol Immunol. 1992;179:121–36. Epub 1992/01/01. 1499346.
9. Kastrukoff LF, Lau AS, Puterman ML, Genetics of natural resistance to herpes simplex virus type 1 latent infection of the peripheral nervous system in mice. J Gen Virol. 1986;67 (Pt 4):613–21. Epub 1986/04/01. 3007658.
10. Lopez C, Genetics of natural resistance to herpesvirus infections in mice. Nature. 1975;258(5531):152–3. Epub 1975/11/13. 171586.
11. Lundberg P, Welander P, Openshaw H, Nalbandian C, Edwards C, Moldawer L, et al. A locus on mouse chromosome 6 that determines resistance to herpes simplex virus also influences reactivation, while an unlinked locus augments resistance of female mice. J Virol. 2003;77(21):11661–73. Epub 2003/10/15. 14557652.
12. Pollara G, Katz DR, Chain BM, The host response to herpes simplex virus infection. Curr Opin Infect Dis. 2004;17(3):199–203. Epub 2004/05/29. doi: 00001432-200406000-00005 [pii]. 15166821.
13. Streilein JW, Dana MR, Ksander BR, Immunity causing blindness: five different paths to herpes stromal keratitis. Immunol Today. 1997;18(9):443–9. Epub 1997/09/18. doi: S0167569997011146 [pii]. 9293161.
14. Stulting RD, Kindle JC, Nahmias AJ, Patterns of herpes simplex keratitis in inbred mice. Invest Ophthalmol Vis Sci. 1985;26(10):1360–7. Epub 1985/10/01. 4044164.
15. Thompson RL, Williams RW, Kotb M, Sawtell NM, A forward phenotypically driven unbiased genetic analysis of host genes that moderate herpes simplex virus virulence and stromal keratitis in mice. PLoS One. 2014;9(3):e92342. Epub 2014/03/22. doi: 10.1371/journal.pone.0092342 PONE-D-13-51634 [pii]. 24651695; PubMed Central PMCID: PMC3961320.
16. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, et al. TLR3 deficiency in patients with Herpes simplex encephalitis. Science. 2007;317(5844):1522–7. Epub 2007/09/18. doi: 317/5844/1522 [pii] doi: 10.1126/science.113952217872438.
17. Brandt CR, Grau DR, Mixed infection with herpes simplex virus type 1 generates recombinants with increased ocular and neurovirulence. Invest Ophthalmol Vis Sci. 1990;31(11):2214–23. 2173682.
18. Zemanick MC, Strick PL, Dix RD, Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain-dependent. Proc Natl Acad Sci U S A. 1991;88(18):8048–51. Epub 1991/09/15. 1654557; PubMed Central PMCID: PMC52443.
19. Wander AH, Centifanto YM, Kaufman HE, Strain specificity of clinical isolates of herpes simplex virus. Arch Ophthalmol. 1980;98:1458–61. 6251792
20. Richards JT, Kern ER, Overall JCJ, Glasgow LA, Differences in neurovirulence among isolates of herpes simplex virus types 1 and 2 in mice using four routes of infection. J Infect Dis. 1981;144:464–71. 6273475
21. Dix RD, McKendall RR, Baringer JR, Comparative neurovirulence of herpes simplex virus type 1 strains after peripheral or intracerebral inoculation of BALB/c mice. Infect Immun. 1983;40:103–12. 6299955
22. Norose K, Yano A, Zhang X-M, Blankenhorn E, Heber-Katz E, Mapping of genes involved in murine herpes simplex virus keratitis: Identification of genes and their modifiers. J Virol. 2002;76:3502–10. 11884574
23. Caignard G, Leiva-Torres GA, Leney-Greene M, Charbonneau B, Dumaine A, Fodil-Cornu N, et al. Genome-wide mouse mutagenesis reveals CD45-mediated T cell function as critical in protective immunity to HSV-1. PLoS Pathog. 2013;9(9):e1003637. Epub 2013/09/27. doi: 10.1371/journal.ppat.1003637 PPATHOGENS-D-13-00829 [pii]. 24068938; PubMed Central PMCID: PMC3771889.
24. Abdelmagid N, Bereczky-Veress B, Guerreiro-Cacais AO, Bergman P, Luhr KM, Bergstrom T, et al. The calcitonin receptor gene is a candidate for regulation of susceptibility to herpes simplex type 1 neuronal infection leading to encephalitis in rat. PLoS Pathog. 2012;8(6):e1002753. Epub 2012/07/05. doi: 10.1371/journal.ppat.1002753 PPATHOGENS-D-11-02597 [pii]. 22761571; PubMed Central PMCID: PMC3386237.
25. Kastrukoff LF, Lau AS, Takei F, Carbone FR, Scalzo AA, A NK complex-linked locus restricts the spread of herpes simplex virus type 1 in the brains of C57BL/6 mice. Immunol Cell Biol. 2015. Epub 2015/05/15. doi: 10.1038/icb.2015.54 icb201554 [pii]. 25971711.
26. Grau DR, Visalli RJ, Brandt CR, Herpes simplex virus stromal keratitis is not titer-dependent and does not correlate with neurovirulence. Invest Ophthalmol Vis Sci. 1989;30(12):2474–80. 2556353.
27. Williams LE, Nesburn AB, Kaufman HE, Experimental induction of disciform keratitis. Arch Ophthalmol. 1965;73:112. 14223669
28. Wildy P, Recombination with herpes simplex virus. J Gen Microbiol. 1955;13(2):346–60. Epub 1955/10/01. doi: 10.1099/00221287-13-2-34613278484.
29. Javier RT, Sedarati F, Stevens JG, Two avirulent herpes simplex viruses generate lethal recombinants in vivo. Science. 1986;234:746–8. 3022376
30. Kintner RL, Allan RW, Brandt CR, Recombinants are isolated at high frequency following in vivo mixed ocular infection with two avirulent herpes simplex virus type 1 strains. Arch Virol. 1995;140(2):231–44. Epub 1995/01/01. 7710352.
31. Lingen M, Hengerer F, Falke D, Mixed vaginal infections of Balb/c mice with low virulent herpes simplex type 1 strains result in restoration of virulence properties: vaginitis/vulvitis and neuroinvasiveness. Med Microbiol Immunol. 1997;185(4):217–22. Epub 1997/03/01. 9138293.
32. Brandt CR, Kolb AW, Shah DD, Pumfery AM, Kintner RL, Jaehnig E, et al. Multiple determinants contribute to the virulence of HSV ocular and CNS infection and identification of serine 34 of the US1 gene as an ocular disease determinant. Invest Ophthalmol Vis Sci. 2003;44(6):2657–68. Epub 2003/05/27. 12766070.
33. Brandt CR, Kolb AW, Tyrosine 116 of the herpes simplex virus type 1 IEalpha22 protein is an ocular virulence determinant and potential phosphorylation site. Invest Ophthalmol Vis Sci. 2003;44(11):4601–7. Epub 2003/10/28. 14578374.
34. Lee K, Kolb AW, Sverchkov Y, Cuellar JA, Craven M, Brandt CR, Recombination analysis of Herpes simplex virus Type 1 reveals a bias towards GC content and the inverted repeat regions. J Virol. 2015. Epub 2015/05/01. doi: JVI.00880-15 [pii] doi: 10.1128/JVI.00880-1525926637.
35. Brandt CR, Coakley LM, Grau DR, A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing. J Virol Methods. 1992;36(3):209–22. 1560105.
36. Kolb AW, Adams M, Cabot EL, Craven M, Brandt CR, Multiplex sequencing of seven ocular Herpes simplex virus Type-1 genomes: Phylogeny, sequence variability and SNP distribution. Invest Ophthalmol Vis Sci. 2011;52:9061–73. PubMed Central PMCID: PMCPMC3231845. doi: 10.1167/iovs.11-781222016062
37. Szpara ML, Gatherer D, Ochoa A, Greenbaum B, Dolan A, Bowden RJ, et al. Evolution and diversity in human herpes simplex virus genomes. J Virol. 2014;88(2):1209–27. Epub 2013/11/15. doi: 10.1128/JVI.01987-13 JVI.01987-13 [pii]. 24227835; PubMed Central PMCID: PMC3911644.
38. Szpara ML, Parsons L, Enquist LW, Sequence variability in clinical and laboratory isolates of herpes simplex virus 1 reveals new mutations. J Virol. 2010;84(10):5303–13. doi: 10.1128/JVI.00312-1020219902
39. Katoh K, Misawa K, Kuma K, Miyata T, MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 2002;30(14):3059–66. Epub 2002/07/24. 12136088; PubMed Central PMCID: PMC135756.
40. Liu K, Raghavan S, Nelesen S, Linder CR, Warnow T, Rapid and accurate large-scale coestimation of sequence alignments and phylogenetic trees. Science. 2009;324(5934):1561–4. Epub 2009/06/23. doi: 10.1126/science.1171243 324/5934/1561 [pii]. 19541996.
41. Breiman L, Random Forests. Machine Learning. 2001;45(1):5–32. doi: 10.1023/A:1010933404324
42. Tibshirani R, Regression Shrinkage and Selection via the Lasso. J Roy Stat Soc B Met. 1996;58(1):267–88.
43. Hoerl AE, Kennard RW, Ridge Regression: Biased Estimation for Nonorthogonal Problems. Technometrics. 1970;12(1):55–67.
44. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504. Epub 2003/11/05. doi: 10.1101/gr.1239303 13/11/2498 [pii]. 14597658; PubMed Central PMCID: PMC403769.
45. Pereira RA, Scalzo A, Simmons A, Cutting edge: a NK complex-linked locus governs acute versus latent herpes simplex virus infection of neurons. J Immunol. 2001;166(10):5869–73. Epub 2001/05/09. 11342599.
46. Freistadt MS, Eberle KE, Correlation between poliovirus type 1 Mahoney replication in blood cells and neurovirulence. J Virol. 1996;70(9):6486–92. Epub 1996/09/01. 8709287; PubMed Central PMCID: PMC190685.
47. Furio V, Garijo R, Duran M, Moya A, Bell JC, Sanjuan R, Relationship between within-host fitness and virulence in the vesicular stomatitis virus: correlation with partial decoupling. J Virol. 2012;86(22):12228–36. Epub 2012/09/07. doi: 10.1128/JVI.00755-12 JVI.00755-12 [pii]. 22951843; PubMed Central PMCID: PMC3486475.
48. Dunn JR, Auten K, Heidari M, Buscaglia C, Correlation between Marek's disease virus pathotype and replication. Avian Dis. 2014;58(2):287–92. Epub 2014/07/25. 25055634.
49. Zhou C, Knipe DM, Association of herpes simplex virus type 1 ICP8 and ICP27 proteins with cellular RNA polymerase II holoenzyme. J Virol. 2002;76(12):5893–904. Epub 2002/05/22. 12021322; PubMed Central PMCID: PMC136207.
50. Esclatine A, Taddeo B, Roizman B, The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs. Proc Natl Acad Sci U S A. 2004;101(52):18165–70. Epub 2004/12/15. doi: 0408272102 [pii] doi: 10.1073/pnas.040827210215596716; PubMed Central PMCID: PMC539803.
51. Kalamvoki M, Roizman B, The histone acetyltransferase CLOCK is an essential component of the herpes simplex virus 1 transcriptome that includes TFIID, ICP4, ICP27, and ICP22. J Virol. 2011;85(18):9472–7. Epub 2011/07/08. doi: 10.1128/JVI.00876-11 JVI.00876-11 [pii]. 21734043; PubMed Central PMCID: PMC3165755.
52. Shu M, Taddeo B, Roizman B, Tristetraprolin Recruits the Herpes Simplex Virion Host Shutoff RNase to AU-Rich Elements in Stress Response mRNAs To Enable Their Cleavage. J Virol. 2015;89(10):5643–50. Epub 2015/03/13. doi: 10.1128/JVI.00091-15 JVI.00091-15 [pii]. 25762736; PubMed Central PMCID: PMC4442522.
53. Taddeo B, Zhang W, Roizman B, Role of herpes simplex virus ICP27 in the degradation of mRNA by virion host shutoff RNase. J Virol. 2010;84(19):10182–90. Epub 2010/07/16. doi: 10.1128/JVI.00975-10 JVI.00975-10 [pii]. 20631134; PubMed Central PMCID: PMC2937800.
54. Shu M, Taddeo B, Zhang W, Roizman B, Selective degradation of mRNAs by the HSV host shutoff RNase is regulated by the UL47 tegument protein. Proc Natl Acad Sci U S A. 2013;110(18):E1669–75. Epub 2013/04/17. doi: 10.1073/pnas.1305475110 1305475110 [pii]. 23589852; PubMed Central PMCID: PMC3645526.
55. Diaz-Moreno I, Hollingworth D, Frenkiel TA, Kelly G, Martin S, Howell S, et al. Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding. Nat Struct Mol Biol. 2009;16(3):238–46. Epub 2009/02/10. doi: 10.1038/nsmb.1558 nsmb.1558 [pii]. 19198587; PubMed Central PMCID: PMC2858377.
56. Wyrwicz LS, Rychlewski L, Fold recognition insights into function of herpes ICP4 protein. Acta Biochim Pol. 2007;54(3):551–9. Epub 2007/09/21. doi: 20071493 [pii]. 17882324.
57. Allen KE, Everett RD, Mutations which alter the DNA binding properties of the herpes simplex virus type 1 transactivating protein Vmw175 also affect its ability to support virus replication. J Gen Virol. 1997;78 (Pt 11):2913–22. Epub 1997/11/21. doi: 10.1099/0022-1317-78-11-29139367379.
58. Ushijima Y, Goshima F, Kimura H, Nishiyama Y, Herpes simplex virus type 2 tegument protein UL56 relocalizes ubiquitin ligase Nedd4 and has a role in transport and/or release of virions. Virol J. 2009;6:168. Epub 2009/10/20. doi: 10.1186/1743-422X-6-168 1743-422X-6-168 [pii]. 19835589; PubMed Central PMCID: PMC2770495.
59. Koshizuka T, Goshima F, Takakuwa H, Nozawa N, Daikoku T, Koiwai O, et al. Identification and characterization of the UL56 gene product of herpes simplex virus type 2. J Virol. 2002;76(13):6718–28. Epub 2002/06/07. 12050385; PubMed Central PMCID: PMC136277.
60. Lau SY, Crump CM, HSV-1 gM and the gK/pUL20 complex are important for the localization of gD and gH/L to viral assembly sites. Viruses. 2015;7(3):915–38. Epub 2015/03/10. doi: 10.3390/v7030915 v7030915 [pii]. 25746217; PubMed Central PMCID: PMC4379555.
61. Foster TP, Chouljenko VN, Kousoulas KG, Functional and physical interactions of the herpes simplex virus type 1 UL20 membrane protein with glycoprotein K. J Virol. 2008;82(13):6310–23. Epub 2008/04/25. doi: 10.1128/JVI.00147-08 JVI.00147-08 [pii]. 18434401; PubMed Central PMCID: PMC2447060.
62. Maruzuru Y, Shindo K, Liu Z, Oyama M, Kozuka-Hata H, Arii J, et al. Role of herpes simplex virus 1 immediate early protein ICP22 in viral nuclear egress. J Virol. 2014;88(13):7445–54. Epub 2014/04/18. doi: 10.1128/JVI.01057-14 JVI.01057-14 [pii]. 24741100; PubMed Central PMCID: PMC4054440.
63. Liu Z, Kato A, Shindo K, Noda T, Sagara H, Kawaoka Y, et al. Herpes simplex virus 1 UL47 interacts with viral nuclear egress factors UL31, UL34, and Us3 and regulates viral nuclear egress. J Virol. 2014;88(9):4657–67. Epub 2014/02/14. doi: 10.1128/JVI.00137-14 JVI.00137-14 [pii]. 24522907; PubMed Central PMCID: PMC3993843.
64. Koyanagi N, Imai T, Arii J, Kato A, Kawaguchi Y, Role of herpes simplex virus 1 Us3 in viral neuroinvasiveness. Microbiol Immunol. 2014;58(1):31–7. Epub 2013/11/10. doi: 10.1111/1348-0421.1210824200420.
65. Kato A, Shindo K, Maruzuru Y, Kawaguchi Y, Phosphorylation of a herpes simplex virus 1 dUTPase by a viral protein kinase, Us3, dictates viral pathogenicity in the central nervous system but not at the periphery. J Virol. 2014;88(5):2775–85. Epub 2013/12/20. doi: 10.1128/JVI.03300-13 JVI.03300-13 [pii]. 24352467; PubMed Central PMCID: PMC3958095.
66. Wang K, Ni L, Wang S, Zheng C, Herpes simplex virus 1 protein kinase US3 hyperphosphorylates p65/RelA and dampens NF-kappaB activation. J Virol. 2014;88(14):7941–51. Epub 2014/05/09. doi: 10.1128/JVI.03394-13 JVI.03394-13 [pii]. 24807716; PubMed Central PMCID: PMC4097809.
67. Wang S, Wang K, Lin R, Zheng C, Herpes simplex virus 1 serine/threonine kinase US3 hyperphosphorylates IRF3 and inhibits beta interferon production. J Virol. 2013;87(23):12814–27. Epub 2013/09/21. doi: 10.1128/JVI.02355-13 JVI.02355-13 [pii]. 24049179; PubMed Central PMCID: PMC3838156.
68. Yang Y, Wu S, Wang Y, Pan S, Lan B, Liu Y, et al. The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein. J Biol Chem. 2015;290(25):15670–8. Epub 2015/04/25. doi: 10.1074/jbc.M115.646422 M115.646422 [pii]. 25907557.
69. Wang X, Patenode C, Roizman B, US3 protein kinase of HSV-1 cycles between the cytoplasm and nucleus and interacts with programmed cell death protein 4 (PDCD4) to block apoptosis. Proc Natl Acad Sci U S A. 2011;108(35):14632–6. Epub 2011/08/17. doi: 10.1073/pnas.1111942108 1111942108 [pii]. 21844356; PubMed Central PMCID: PMC3167522.
70. Viejo-Borbolla A, Martinez-Martin N, Nel HJ, Rueda P, Martin R, Blanco S, et al. Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses. PLoS Pathog. 2012;8(2):e1002497. Epub 2012/02/10. doi: 10.1371/journal.ppat.1002497 PPATHOGENS-D-11-01352 [pii]. 22319442; PubMed Central PMCID: PMC3271085.
71. Chee AV, Roizman B, Herpes simplex virus 1 gene products occlude the interferon signaling pathway at multiple sites. J Virol. 2004;78(8):4185–96. Epub 2004/03/30. 15047834; PubMed Central PMCID: PMC374303.
72. Eisemann J, Muhl-Zurbes P, Steinkasserer A, Kummer M, Infection of mature dendritic cells with herpes simplex virus type 1 interferes with the interferon signaling pathway. Immunobiology. 2007;212(9–10):877–86. Epub 2007/12/19. doi: S0171-2985(07)00110-6 [pii] doi: 10.1016/j.imbio.2007.09.00518086386.
73. Melchjorsen J, Siren J, Julkunen I, Paludan SR, Matikainen S, Induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by ICP27 targeting NF-kappaB and IRF-3. J Gen Virol. 2006;87(Pt 5):1099–108. 16603509.
74. Kim JC, Lee SY, Kim SY, Kim JK, Kim HJ, Lee HM, et al. HSV-1 ICP27 suppresses NF-kappaB activity by stabilizing IkappaBalpha. FEBS Lett. 2008;582(16):2371–6. Epub 2008/06/10. doi: 10.1016/j.febslet.2008.05.044 S0014-5793(08)00474-2 [pii]. 18539148.