9. Kalverda AP, Thompson GS, Vogel A, Schroder M, Bowie AG, et al. (2009) Poxvirus K7 protein adopts a Bcl-2 fold: biochemical mapping of its interactions with human DEAD box RNA helicase DDX3. J Mol Biol 385: 843–853. 10. Oda S, Schroder M, Khan AR (2009) Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7. Structure 17: 1528–1537. 11. Schroder M, Baran M, Bowie AG (2008) Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J 27: 2147–2157. 12. Stack J, Haga IR, Schroder M, Bartlett NW, Maloney G, et al. (2005) Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. J Exp Med 201: 1007–1018. 13. Chung CS, Chen CH, Ho MY, Huang CY, Liao CL, et al. (2006) Vaccinia virus proteome: identification of proteins in vaccinia virus intracellular mature virion particles. J Virol 80: 2127–2140. 14. Zhang L, Villa NY, Rahman MM, Smallwood S, Shattuck D, et al. (2009) Analysis of vaccinia virus-host protein-protein interactions: validations of yeast two-hybrid screenings. J Proteome Res 8: 4311–4318. 15. Oseroff C, Peters B, Pasquetto V, Moutaftsi M, Sidney J, et al. (2008) Dissociation between epitope hierarchy and immunoprevalence in CD8 responses to vaccinia virus western reserve. J Immunol 180: 7193–7202. 16. Esteban M (2009) Attenuated poxvirus vectors MVA and NYVAC as promising vaccine candidates against HIV/AIDS. Hum Vaccin 5: 867–871. 17. Garcia-Arriaza J, Najera JL, Gomez CE, Sorzano CO, Esteban M (2010) Immunogenic profiling in mice of a HIV/AIDS vaccine candidate (MVA-B) expressing four HIV-1 antigens and potentiation by specific gene deletions. PLoS One 5: e12395. 18. Gomez CE, Najera JL, Jimenez EP, Jimenez V, Wagner R, et al. (2007) Head- to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co- expressing in a single locus the HIV-1BX08 gp120 and HIV-1(IIIB) Gag-Pol- Nef proteins of clade B. Vaccine 25: 2863–2885. 19. Gomez CE, Najera JL, Jimenez V, Bieler K, Wild J, et al. (2007) Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/ Gag-Pol-Nef antigens of clade C. Vaccine 25: 1969–1992. 20. Gomez CE, Najera JL, Sanchez R, Jimenez V, Esteban M (2009) Multimeric soluble CD40 ligand (sCD40L) efficiently enhances HIV specific cellular immune responses during DNA prime and boost with attenuated poxvirus vectors MVA and NYVAC expressing HIV antigens. Vaccine 27: 3165–3174. 21. Harari A, Bart PA, Stohr W, Tapia G, Garcia M, et al. (2008) An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med 205: 63–77. 22. Mooij P, Balla-Jhagjhoorsingh SS, Koopman G, Beenhakker N, van Haaften P, et al. (2008) Differential CD4+ versus CD8+ T-cell responses elicited by different poxvirus-based human immunodeficiency virus type 1 vaccine candidates provide comparable efficacies in primates. J Virol 82: 2975–2988. 23. Gomez CE, Najera JL, Krupa M, Esteban M (2008) The poxvirus vectors MVA and NYVAC as gene delivery systems for vaccination against infectious diseases and cancer. Curr Gene Ther 8: 97–120. 24. Guerra S, Gonzalez JM, Climent N, Reyburn H, Lopez-Fernandez LA, et al. (2010) Selective induction of host genes by MVA-B, a candidate vaccine against HIV/AIDS. J Virol 84: 8141–8152. 25. Climent N, Guerra S, Garcia F, Rovira C, Miralles L, et al. (2011) Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1- Specific CD8 T Cell Responses in HIV-1-Infected Individuals. PLoS One 6: e19644. 26. Guerra S, Najera JL, Gonzalez JM, Lopez-Fernandez LA, Climent N, et al. (2007) Distinct gene expression profiling after infection of immature human monocyte-derived dendritic cells by the attenuated poxvirus vectors MVA and NYVAC. J Virol 81: 8707–8721. 27. Amara RR, Villinger F, Staprans SI, Altman JD, Montefiori DC, et al. (2002) Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA/MVA vaccines. J Virol 76: 7625–7631. 28. Barouch DH, Santra S, Schmitz JE, Kuroda MJ, Fu TM, et al. (2000) Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine- augmented DNA vaccination. Science 290: 486–492. 29. Robinson HL, Sharma S, Zhao J, Kannanganat S, Lai L, et al. (2007) Immunogenicity in macaques of the clinical product for a clade B DNA/MVA HIV vaccine: elicitation of IFN-gamma, IL-2, and TNF-alpha coproducing CD4 and CD8 T cells. AIDS Res Hum Retroviruses 23: 1555–1562. 30. Champagne P, Ogg GS, King AS, Knabenhans C, Ellefsen K, et al. (2001) Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410: 106–111. 31. Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22: 745–763. 32. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401: 708–712. 33. Seder RA, Darrah PA, Roederer M (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8: 247–258. 34. Perdiguero B, Esteban M (2009) The interferon system and vaccinia virus evasion mechanisms. J Interferon Cytokine Res 29: 581–598. C6L Deletion in MVA-B Improves HIV Immunogenicity 35. Girgis NM, Dehaven BC, Xiao Y, Alexander E, Viner KM, et al. (2011) The Vaccinia virus complement control protein modulates adaptive immune responses during infection. J Virol 85: 2547–2556. 36. Rehm KE, Roper RL (2011) Deletion of the A35 gene from Modified Vaccinia Virus Ankara increases immunogenicity and isotype switching. Vaccine 29: 3276–3283. 37. Cottingham MG, Andersen RF, Spencer AJ, Saurya S, Furze J, et al. (2008) Recombination-mediated genetic engineering of a bacterial artificial chromo- some clone of modified vaccinia virus Ankara (MVA). PLoS One 3: e1638. 38. Clark RH, Kenyon JC, Bartlett NW, Tscharke DC, Smith GL (2006) Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy. J Gen Virol 87: 29–38. 39. Staib C, Kisling S, Erfle V, Sutter G (2005) Inactivation of the viral interleukin 1beta receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara. J Gen Virol 86: 1997–2006. 40. Delaloye J, Roger T, Steiner-Tardivel QG, Le Roy D, Knaup Reymond M, et al. (2009) Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by TLR2-TLR6, MDA-5 and the NALP3 inflammasome. PLoS Pathog 5: e1000480. 41. Perfetto SP, Chattopadhyay PK, Roederer M (2004) Seventeen-colour flow cytometry: unravelling the immune system. Nat Rev Immunol 4: 648–655. 42. Addo MM, Draenert R, Rathod A, Verrill CL, Davis BT, et al. (2007) Fully differentiated HIV-1 specific CD8+ T effector cells are more frequently detectable in controlled than in progressive HIV-1 infection. PLoS One 2: e321. 43. Hess C, Altfeld M, Thomas SY, Addo MM, Rosenberg ES, et al. (2004) HIV-1 specific CD8+ T cells with an effector phenotype and control of viral replication. Lancet 363: 863–866. 44. Northfield JW, Loo CP, Barbour JD, Spotts G, Hecht FM, et al. (2007) Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T(EMRA) cells in early infection are linked to control of HIV-1 viremia and predict the subsequent viral load set point. J Virol 81: 5759–5765. 45. Currier JR, Ngauy V, de Souza MS, Ratto-Kim S, Cox JH, et al. (2010) Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine candidate. PLoS One 5: e13983. 46. Bart PA, Goodall R, Barber T, Harari A, Guimaraes-Walker A, et al. (2008) EV01: a phase I trial in healthy HIV negative volunteers to evaluate a clade C HIV vaccine, NYVAC-C undertaken by the EuroVacc Consortium. Vaccine 26: 3153–3161. 47. McCormack S, Stohr W, Barber T, Bart PA, Harari A, et al. (2008) EV02: a Phase I trial to compare the safety and immunogenicity of HIV DNA-C prime- NYVAC-C boost to NYVAC-C alone. Vaccine 26: 3162–3174. 48. Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, et al. (2007) CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 13: 46–53. 49. Wilson NA, Keele BF, Reed JS, Piaskowski SM, MacNair CE, et al. (2009) Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge. J Virol 83: 6508–6521. 50. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, et al. (2006) HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107: 4781–4789. 51. Harari A, Petitpierre S, Vallelian F, Pantaleo G (2004) Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy. Blood 103: 966–972. 52. Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB (1994) Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68: 6103–6110. 53. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, et al. (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68: 4650–4655. 54. Amara RR, Ibegbu C, Villinger F, Montefiori DC, Sharma S, et al. (2005) Studies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89.6P challenge in DNA/ MVA-vaccinated macaques. Virology 343: 246–255. 55. Harari A, Vallelian F, Meylan PR, Pantaleo G (2005) Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence. J Immunol 174: 1037–1045. 56. Younes SA, Yassine-Diab B, Dumont AR, Boulassel MR, Grossman Z, et al. (2003) HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J Exp Med 198: 1909–1922. 57. Zimmerli SC, Harari A, Cellerai C, Vallelian F, Bart PA, et al. (2005) HIV-1- specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells. Proc Natl Acad Sci U S A 102: 7239–7244. 58. Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, et al. (2009) Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med 15: 293–299. 59. Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, et al. (2011) Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473: 523–527. PLoS ONE | www.plosone.org 13 August 2011 | Volume 6 | Issue 8 | e24244