T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence

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We discovered that the largest gene in the genome of monkeypox viruses and several related viruses, including the virus causing smallpox, but not vaccine strains, encode a protein (B22) that renders the cellular immune system non-responsive. A particularly novel aspect of this work is that B22 proteins directly disable cells of the immune system as compared to previously known molecular strategies that help viruses to hide from the immune system. We further show that monkeypox viruses containing this protein are much more virulent in non-human primates than viruses that lack B22. Our observations suggest that B22 proteins contribute to monkeypox virulence and might have contributed to the severe disease manifestations of variola major virus. However, these data also suggest that B22 proteins could potentially be used to curb undesired immune responses such as autoimmunity or graft versus host disease.

Vyšlo v časopise: T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004123
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004123

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Zdroje

1. GrossE (2003) Update on emerging infections: news from the Centers for Disease Control and prevention. Update: Multistate outbreak of monkeypox–Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. Ann Emerg Med 42: 660–662 discussion 662–664.

2. LikosAM, SammonsSA, OlsonVA, FraceAM, LiY, et al. (2005) A tale of two clades: monkeypox viruses. J Gen Virol 86: 2661–2672.

3. ChenN, LiG, LiszewskiMK, AtkinsonJP, JahrlingPB, et al. (2005) Virulence differences between monkeypox virus isolates from West Africa and the Congo basin. Virology 340: 46–63.

4. HutsonCL, OlsonVA, CarrollDS, AbelJA, HughesCM, et al. (2009) A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus. J Gen Virol 90: 323–333.

5. SbranaE, XiaoSY, NewmanPC, TeshRB (2007) Comparative pathology of North American and central African strains of monkeypox virus in a ground squirrel model of the disease. Am J Trop Med Hyg 76: 155–164.

6. SaijoM, AmiY, SuzakiY, NagataN, IwataN, et al. (2009) Virulence and pathophysiology of the Congo Basin and West African strains of monkeypox virus in non-human primates. J Gen Virol 90: 2266–2271.

7. SejvarJJ, ChowdaryY, SchomogyiM, StevensJ, PatelJ, et al. (2004) Human monkeypox infection: a family cluster in the midwestern United States. J Infect Dis 190: 1833–1840.

8. GubserC, HueS, KellamP, SmithGL (2004) Poxvirus genomes: a phylogenetic analysis. J Gen Virol 85: 105–117.

9. HammarlundE, LewisMW, CarterSV, AmannaI, HansenSG, et al. (2005) Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat Med 11: 1005–1011.

10. HammarlundE, LewisMW, HansenSG, StrelowLI, NelsonJA, et al. (2003) Duration of antiviral immunity after smallpox vaccination. Nat Med 9: 1131–1137.

11. Edghill-SmithY, GoldingH, ManischewitzJ, KingLR, ScottD, et al. (2005) Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat Med 11: 740–747.

12. PanchanathanV, ChaudhriG, KarupiahG (2006) Protective immunity against secondary poxvirus infection is dependent on antibody but not on CD4 or CD8 T-cell function. J Virol 80: 6333–6338.

13. BelyakovIM, EarlP, DzutsevA, KuznetsovVA, LemonM, et al. (2003) Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Proc Natl Acad Sci U S A 100: 9458–9463.

14. SnyderJT, BelyakovIM, DzutsevA, LemonnierF, BerzofskyJA (2004) Protection against lethal vaccinia virus challenge in HLA-A2 transgenic mice by immunization with a single CD8+ T-cell peptide epitope of vaccinia and variola viruses. J Virol 78: 7052–7060.

15. TscharkeDC, KarupiahG, ZhouJ, PalmoreT, IrvineKR, et al. (2005) Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines. J Exp Med 201: 95–104.

16. GrandpreLE, Duke-CohanJS, EwaldBA, DevoyC, BarouchDH, et al. (2009) Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys. Vaccine 27: 1549–1556.

17. EarlPL, AmericoJL, WyattLS, EllerLA, MontefioriDC, et al. (2007) Recombinant modified vaccinia virus Ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate. Virology 366: 84–97.

18. ByunM, VerweijMC, PickupDJ, WiertzEJ, HansenTH, et al. (2009) Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells. Cell Host Microbe 6: 422–432.

19. ByunM, WangX, PakM, HansenTH, YokoyamaWM (2007) Cowpox virus exploits the endoplasmic reticulum retention pathway to inhibit MHC class I transport to the cell surface. Cell Host Microbe 2: 306–315.

20. AlzhanovaD, EdwardsDM, HammarlundE, ScholzIG, HorstD, et al. (2009) Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition. Cell Host Microbe 6: 433–445.

21. HammarlundE, DasguptaA, FruehK, SlifkaMK (2008) Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation. Proc Natl Acad Sci U S A 105: 14567–72.

22. DasguptaA, HammarlundE, SlifkaMK, FruhK (2007) Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules. J Immunol 178: 1654–1661.

23. LoffredoJT, BurwitzBJ, RakaszEG, SpencerSP, StephanyJJ, et al. (2007) The antiviral efficacy of simian immunodeficiency virus-specific CD8+ T cells is unrelated to epitope specificity and is abrogated by viral escape. J Virol 81: 2624–2634.

24. YangG, PevearDC, DaviesMH, CollettMS, BaileyT, et al. (2005) An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge. J Virol 79: 13139–13149.

25. LewinsohnDA, WinataE, SwarbrickGM, TannerKE, CookMS, et al. (2007) Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B. PLoS Pathog 3: 1240–1249.

26. HeinzelAS, GrotzkeJE, LinesRA, LewinsohnDA, McNabbAL, et al. (2002) HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells. J Exp Med 196: 1473–1481.

27. EstepRD, MessaoudiI, O'ConnorMA, LiH, SpragueJ, et al. (2011) Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection. J Virol 85: 9527–9542.

28. HorstD, VerweijMC, DavisonAJ, RessingME, WiertzEJ (2011) Viral evasion of T cell immunity: ancient mechanisms offering new applications. Curr Opin Immunol 23: 96–103.

29. AlcamiA, LiraSA (2010) Modulation of chemokine activity by viruses. Curr Opin Immunol 22: 482–487.

30. SmithVP, BryantNA, AlcamiA (2000) Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins. J Gen Virol 81: 1223–1230.

31. Smith GL, Symons JA, Alcami A (1999) Immune modulation by proteins secreted from cells infected by vaccinia virus. Arch Virol Suppl 15: : 111–129.

32. NashP, BarrettJ, CaoJX, Hota-MitchellS, LalaniAS, et al. (1999) Immunomodulation by viruses: the myxoma virus story. Immunol Rev 168: 103–120.

33. SaraivaM, SmithP, FallonPG, AlcamiA (2002) Inhibition of type 1 cytokine-mediated inflammation by a soluble CD30 homologue encoded by ectromelia (mousepox) virus. J Exp Med 196: 829–839.

34. LiH, DeetzCO, ZapataJC, CairoC, HebbelerAM, et al. (2007) Vaccinia virus inhibits T cell receptor-dependent responses by human gammadelta T cells. J Infect Dis 195: 37–45.

35. GabaevI, SteinbruckL, PokoyskiC, PichA, StantonRJ, et al. (2011) The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells. PLoS Pathog 7: e1002432.

36. BesoldK, WillsM, PlachterB (2009) Immune evasion proteins gpUS2 and gpUS11 of human cytomegalovirus incompletely protect infected cells from CD8 T cell recognition. Virology 391: 5–19.

37. HuangJ, BrameshuberM, ZengX, XieJ, LiQJ, et al. (2013) A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells. Immunity 39: 846–857.

38. McGrathMM, NajafianN (2012) The role of coinhibitory signaling pathways in transplantation and tolerance. Front Immunol 3: 47.

39. SmithGL, McFaddenG (2002) Smallpox: anything to declare? Nat Rev Immunol 2: 521–527.

40. GuerinJL, GelfiJ, BoullierS, DelverdierM, BellangerFA, et al. (2002) Myxoma virus leukemia-associated protein is responsible for major histocompatibility complex class I and Fas-CD95 down-regulation and defines scrapins, a new group of surface cellular receptor abductor proteins. J Virol 76: 2912–2923.

41. FrebelH, RichterK, OxeniusA (2010) How chronic viral infections impact on antigen-specific T-cell responses. Eur J Immunol 40: 654–663.

42. TardifJC, L'AllierPL, GregoireJ, IbrahimR, McFaddenG, et al. (2010) A randomized controlled, phase 2 trial of the viral serpin Serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Circ Cardiovasc Interv 3: 543–548.

43. HrubyDE, GuarinoLA, KatesJR (1979) Vaccinia virus replication. I. Requirement for the host-cell nucleus. J Virol 29: 705–715.

44. AltschulerY, BarbasSM, TerleckyLJ, TangK, HardyS, et al. (1998) Redundant and distinct functions for dynamin-1 and dynamin-2 isoforms. J Cell Biol 143: 1871–1881.

45. StreblowDN, Soderberg-NauclerC, VieiraJ, SmithP, WakabayashiE, et al. (1999) The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell 99: 511–520.

46. BoyleDB, CouparBE (1988) A dominant selectable marker for the construction of recombinant poxviruses. Gene 65: 123–128.

47. HortonRM, HuntHD, HoSN, PullenJK, PeaseLR (1989) Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 77: 61–68.

48. CameronCM, BarrettJW, MannM, LucasA, McFaddenG (2005) Myxoma virus M128L is expressed as a cell surface CD47-like virulence factor that contributes to the downregulation of macrophage activation in vivo. Virology 337: 55–67.

49. PickupDJ, InkBS, ParsonsBL, HuW, JoklikWK (1984) Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proc Natl Acad Sci U S A 81: 6817–6821.

50. PanusJF, SmithCA, RayCA, SmithTD, PatelDD, et al. (2002) Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue. Proc Natl Acad Sci U S A 99: 8348–8353.

51. MossB, Elroy-SteinO, MizukamiT, AlexanderWA, FuerstTR (1990) Product review. New mammalian expression vectors. Nature 348: 91–92.

52. MackettM, SmithGL, MossB (1984) General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol 49: 857–864.

53. FuerstTR, EarlPL, MossB (1987) Use of a hybrid vaccinia virus-T7 RNA polymerase system for expression of target genes. Mol Cell Biol 7: 2538–2544.

54. VennemaH, RijnbrandR, HeijnenL, HorzinekMC, SpaanWJ (1991) Enhancement of the vaccinia virus/phage T7 RNA polymerase expression system using encephalomyocarditis virus 5'-untranslated region sequences. Gene 108: 201–209.

55. Smith DB, Corcoran LM (2001) Expression and purification of glutathione-S-transferase fusion proteins. Curr Protoc Mol Biol Chapter 16 : Unit16 17.

56. NelsonEK, PiehlerB, EckelsJ, RauchA, BellewM, et al. (2011) LabKey Server: an open source platform for scientific data integration, analysis and collaboration. BMC Bioinformatics 12: 71.

57. LohseM, BolgerAM, NagelA, FernieAR, LunnJE, et al. (2012) RobiNA: a user-friendly, integrated software solution for RNA-Seq-based transcriptomics. Nucleic Acids Res 40: W622–627.

58. LiH, DurbinR (2010) Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26: 589–595.

59. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079.

60. StajichJE, BlockD, BoulezK, BrennerSE, ChervitzSA, et al. (2002) The Bioperl toolkit: Perl modules for the life sciences. Genome Res 12: 1611–1618.