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Prophylactic and Therapeutic Modulation of Innate and Adaptive Immunity Against Mucosal Infection of Herpes Simplex Virus

  • Uyangaa, Erdenebileg (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Patil, Ajit Mahadev (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Eo, Seong Kug (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University)
  • Received : 2014.07.02
  • Accepted : 2014.08.04
  • Published : 2014.08.31
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Abstract

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are the most common cause of genital ulceration in humans worldwide. Typically, HSV-1 and 2 infections via mucosal route result in a lifelong latent infection after peripheral replication in mucosal tissues, thereby providing potential transmission to neighbor hosts in response to reactivation. To break the transmission cycle, immunoprophylactics and therapeutic strategies must be focused on prevention of infection or reduction of infectivity at mucosal sites. Currently, our understanding of the immune responses against mucosal infection of HSV remains intricate and involves a balance between innate signaling pathways and the adaptive immune responses. Numerous studies have demonstrated that HSV mucosal infection induces type I interferons (IFN) via recognition of Toll-like receptors (TLRs) and activates multiple immune cell populations, including NK cells, conventional dendritic cells (DCs), and plasmacytoid DCs. This innate immune response is required not only for the early control of viral replication at mucosal sites, but also for establishing adaptive immune responses against HSV antigens. Although the contribution of humoral immune response is controversial, $CD4^+$ Th1 T cells producing IFN-${\gamma}$ are believed to play an important role in eradicating virus from the hosts. In addition, the recent experimental successes of immunoprophylactic and therapeutic compounds that enhance resistance and/or reduce viral burden at mucosal sites have accumulated. This review focuses on attempts to modulate innate and adaptive immunity against HSV mucosal infection for the development of prophylactic and therapeutic strategies. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses. Thus, we summarized the current evidence of various immune mediators in response to mucosal HSV infection, focusing on the importance of innate immune responses.

Keywords

References

  1. Mansur, D. S., E. G. Kroon, M. L. Nogueira, R. M. Arantes, S. C. Rodrigues, S. Akira, R. T. Gazzinelli, and M. A. Campos. 2005. Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1. Am. J. Pathol. 166: 1419-1426. https://doi.org/10.1016/S0002-9440(10)62359-0
  2. Roizman. B., and Knipe, D. M. 2001. Herpes simplex viruses and their replication. In Fields Virology, 4th edition. Eds. Knipe, D. M., and Howley, P. M. Lippincott Williams & Wilkins. p. 2399-2459.
  3. Ellermann-Eriksen, S. 2005. Macrophages and cytokines in the early defence against herpes simplex virus. Virol. J. 2: 59. https://doi.org/10.1186/1743-422X-2-59
  4. Chan, T., N. G. Barra, A. J. Lee, and A. A. Ashkar. 2011. Innate and adaptive immunity against herpes simplex virus type 2 in the genital mucosa. J. Reprod. Immunol. 88: 210-218. https://doi.org/10.1016/j.jri.2011.01.001
  5. Wakimoto, H., P. R. Johnson, D. M. Knipe, and E. A. Chiocca. 2003. Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells. Gene Ther. 10: 983-990. https://doi.org/10.1038/sj.gt.3302038
  6. Kim, M., N. R. Osborne, W. Zeng, H. Donaghy, K. McKinnon, D. C. Jackson, and A. L. Cunningham. 2012. Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes. J. Immunol. 188: 4158-4170. https://doi.org/10.4049/jimmunol.1103450
  7. Harandi, A. M., B. Svennerholm, J. Holmgren, and K. Eriksson. 2001. Differential roles of B cells and IFN-gamma-secreting CD4(+) T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice. J. Gen. Virol. 82: 845-853. https://doi.org/10.1099/0022-1317-82-4-845
  8. Verschoor, A., M. A. Brockman, D. M. Knipe, and M. C. Carroll. 2001. Cutting edge: myeloid complement C3 enhances the humoral response to peripheral viral infection. J. Immunol. 167: 2446-2451. https://doi.org/10.4049/jimmunol.167.5.2446
  9. Da, C., X, M. A. Brockman, E. Alicot, M. Ma, M. B. Fischer, X. Zhou, D. M. Knipe, and M. C. Carroll. 1999. Humoral response to herpes simplex virus is complement-dependent. Proc. Natl. Acad. Sci. U. S. A. 96: 12708-12712. https://doi.org/10.1073/pnas.96.22.12708
  10. Kwant-Mitchell, A., A. A. Ashkar, and K. L. Rosenthal. 2009. Mucosal innate and adaptive immune responses against herpes simplex virus type 2 in a humanized mouse model. J. Virol. 83: 10664-10676. https://doi.org/10.1128/JVI.02584-08
  11. Gebhardt, B. M., F. Focher, R. Eberle, A. Manikowski, and G. E. Wright. 2009. Effect of combinations of antiviral drugs on herpes simplex encephalitis. Drug Des Devel. Ther. 3: 289-294.
  12. Bourne, K. Z., N. Bourne, S. F. Reising, and L. R. Stanberry. 1999. Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2. Antiviral Res. 42: 219-226. https://doi.org/10.1016/S0166-3542(99)00020-0
  13. Bernstein, D. I., and L. R. Stanberry. 1999. Herpes simplex virus vaccines. Vaccine 17: 1681-1689. https://doi.org/10.1016/S0264-410X(98)00434-4
  14. Kawai, T., and S. Akira. 2005. Pathogen recognition with Toll-like receptors. Curr. Opin. Immunol. 17: 338-344. https://doi.org/10.1016/j.coi.2005.02.007
  15. Takeda, K., T. Kaisho, and S. Akira. 2003. Toll-like receptors. Annu. Rev. Immunol. 21: 335-376. https://doi.org/10.1146/annurev.immunol.21.120601.141126
  16. Kawai, T., and S. Akira. 2007. TLR signaling. Cell Death Differ. 13: 816-825.
  17. Doyle, S. L., and L. A. O'Neill. 2006. Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 72: 1102-1113. https://doi.org/10.1016/j.bcp.2006.07.010
  18. Menasria, R., N. Boivin, M. Lebel, J. Piret, J. Gosselin, and G. Boivin. 2013. Both TRIF and IPS-1 adaptor proteins contribute to the cerebral innate immune response against herpes simplex virus 1 infection. J. Virol. 87: 7301-7308. https://doi.org/10.1128/JVI.00591-13
  19. Wang, J. P., G. N. Bowen, S. Zhou, A. Cerny, A. Zacharia, D. M. Knipe, R. W. Finberg, and E. A. Kurt-Jones. 2012. Role of specific innate immune responses in herpes simplex virus infection of the central nervous system. J. Virol. 86: 2273-2281. https://doi.org/10.1128/JVI.06010-11
  20. Aravalli, R. N., S. Hu, T. N. Rowen, J. M. Palmquist, and J. R. Lokensgard. 2005. Cutting edge: TLR2-mediated proinflammatory cytokine and chemokine production by microglial cells in response to herpes simplex virus. J. Immunol. 175: 4189-4193. https://doi.org/10.4049/jimmunol.175.7.4189
  21. Schachtele, S. J., S. Hu, M. R. Little, and J. R. Lokensgard. 2010. Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2. J. Neuroinflammation. 7: 35. https://doi.org/10.1186/1742-2094-7-35
  22. Krieg, A. M., A. K. Yi, S. Matson, T. J. Waldschmidt, G. A. Bishop, R. Teasdale, G. A. Koretzky, and D. M. Klinman. 1995. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374: 546-459. https://doi.org/10.1038/374546a0
  23. Hochrein, H., B. Schlatter, M. O'Keeffe, C. Wagner, F. Schmitz, M. Schiemann, S. Bauer, M. Suter, and H. Wagner. 2004. Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and -independent pathways. Proc. Natl. Acad. Sci. U. S. A. 101: 11416-11421. https://doi.org/10.1073/pnas.0403555101
  24. Sorensen, L. N., L. S. Reinert, L. Malmgaard, C. Bartholdy, A. R. Thomsen, and S. R. Paludan. 2008. TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain. J. Immunol. 181: 8604-8612. https://doi.org/10.4049/jimmunol.181.12.8604
  25. Krug, A., G. D. Luker, W. Barchet, D. A. Leib, S. Akira, and M. Colonna. 2004. Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 103: 1433-1437.
  26. Tengvall, S., and A. M. Harandi. 2008. Importance of myeloid differentiation factor 88 in innate and acquired immune protection against genital herpes infection in mice. J. Reprod. Immunol. 78: 49-57. https://doi.org/10.1016/j.jri.2007.09.001
  27. Guo, Y., M. Audry, M. Ciancanelli, L. Alsina, J. Azevedo, M. Herman, E. Anguiano, V. Sancho-Shimizu, L. Lorenzo, E. Pauwels, P. B. Philippe, D. R. Perez de, A. Cardon, G. Vogt, C. Picard, Z. Z. Andrianirina, F. Rozenberg, P. Lebon, S. Plancoulaine, M. Tardieu, D. Valerie, E. Jouanguy, D. Chaussabel, F. Geissmann, L. Abel, J. L. Casanova, and S. Y. Zhang. 2011. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J. Exp. Med. 208: 2083-2098. https://doi.org/10.1084/jem.20101568
  28. Reinert, L. S., L. Harder, C. K. Holm, M. B. Iversen, K. A. Horan, F. gnaes-Hansen, B. P. Ulhoi, T. H. Holm, T. H. Mogensen, T. Owens, J. R. Nyengaard, A. R. Thomsen, and S. R. Paludan. 2012. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice. J. Clin. Invest 122: 1368-1376. https://doi.org/10.1172/JCI60893
  29. Swann, J. B., Y. Hayakawa, N. Zerafa, K. C. Sheehan, B. Scott, R. D. Schreiber, P. Hertzog, and M. J. Smyth. 2007. Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. J. Immunol. 178: 7540-7549. https://doi.org/10.4049/jimmunol.178.12.7540
  30. Isaacs, A., J. Lindenmann, and R. C. Valentine. 1957. Virus interference. II. Some properties of interferon. Proc. R. Soc. Lond B Biol. Sci. 147: 268-273. https://doi.org/10.1098/rspb.1957.0049
  31. Liu, Y. J. 2005. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23: 275-306. https://doi.org/10.1146/annurev.immunol.23.021704.115633
  32. Janeway, C. A., Travers, P., Walport, M., and Shlomchik, M. J. 2005. Immunobiology. The immune system in health and disease, 6th Edition. Garland Science, New York, p. 461-516.
  33. Kotenko, S. V., G. Gallagher, V. V. Baurin, A. Lewis-Antes, M. Shen, N. K. Shah, J. A. Langer, F. Sheikh, H. Dickensheets, and R. P. Donnelly. 2003. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4: 69-77.
  34. Sheppard, P., W. Kindsvogel, W. Xu, K. Henderson, S. Schlutsmeyer, T. E. Whitmore, R. Kuestner, U. Garrigues, C. Birks, J. Roraback, C. Ostrander, D. Dong, J. Shin, S. Presnell, B. Fox, B. Haldeman, E. Cooper, D. Taft, T. Gilbert, F. J. Grant, M. Tackett, W. Krivan, G. McKnight, C. Clegg, D. Foster, and K. M. Klucher. 2003. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat. Immunol. 4: 63-68. https://doi.org/10.1038/ni873
  35. Gill, N., P. M. Deacon, B. Lichty, K. L. Mossman, and A. A. Ashkar. 2006. Induction of innate immunity against herpes simplex virus type 2 infection via local delivery of Toll-like receptor ligands correlates with beta interferon production. J. Virol. 80: 9943-9950. https://doi.org/10.1128/JVI.01036-06
  36. Rasmussen, S. B., L. N. Sorensen, L. Malmgaard, N. Ank, J. D. Baines, Z. J. Chen, and S. R. Paludan. 2007. Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through Toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems. J. Virol. 81: 13315-13324. https://doi.org/10.1128/JVI.01167-07
  37. Conrady, C. D., W. P. Halford, and D. J. Carr. 2011. Loss of the type I interferon pathway increases vulnerability of mice to genital herpes simplex virus 2 infection. J. Virol. 85: 1625-1633. https://doi.org/10.1128/JVI.01715-10
  38. Conrady, C. D., H. Jones, M. Zheng, and D. J. Carr. 2011. A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes. J. Biomed. Res. 25: 111-119. https://doi.org/10.1016/S1674-8301(11)60014-6
  39. Conrady, C. D., M. Zheng, N. A. Mandal, R. N. van, and D. J. Carr. 2013. IFN-alpha-driven CCL2 production recruits inflammatory monocytes to infection site in mice. Mucosal. Immunol. 6: 45-55. https://doi.org/10.1038/mi.2012.46
  40. Gill, N., M. J. Chenoweth, E. F. Verdu, and A. A. Ashkar. 2011. NK cells require type I IFN receptor for antiviral responses during genital HSV-2 infection. Cell Immunol. 269: 29-37. https://doi.org/10.1016/j.cellimm.2011.03.007
  41. Milligan, G. N., and D. I. Bernstein. 1997. Interferon-gamma enhances resolution of herpes simplex virus type 2 infection of the murine genital tract. Virology 229: 259-268. https://doi.org/10.1006/viro.1997.8441
  42. Mikloska, Z., and A. L. Cunningham. 2001. Alpha and gamma interferons inhibit herpes simplex virus type 1 infection and spread in epidermal cells after axonal transmission. J. Virol. 75: 11821-11826. https://doi.org/10.1128/JVI.75.23.11821-11826.2001
  43. Dobbs, M. E., J. E. Strasser, C. F. Chu, C. Chalk, and G. N. Milligan. 2005. Clearance of herpes simplex virus type 2 by $CD8^+$ T cells requires gamma interferon and either perforin-or Fas-mediated cytolytic mechanisms. J. Virol. 79: 14546-14554. https://doi.org/10.1128/JVI.79.23.14546-14554.2005
  44. Cantin, E., B. Tanamachi, and H. Openshaw. 1999. Role for gamma interferon in control of herpes simplex virus type 1 reactivation. J. Virol. 73: 3418-3423.
  45. Doyle, S. E., H. Schreckhise, K. Khuu-Duong, K. Henderson, R. Rosler, H. Storey, L. Yao, H. Liu, F. Barahmand-pour, P. Sivakumar, C. Chan, C. Birks, D. Foster, C. H. Clegg, P. Wietzke-Braun, S. Mihm, and K. M. Klucher. 2006. Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes. Hepatology 44: 896-906. https://doi.org/10.1002/hep.21312
  46. Zhou, Z., O. J. Hamming, N. Ank, S. R. Paludan, A. L. Nielsen, and R. Hartmann. 2007. Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases. J. Virol. 81: 7749-7758. https://doi.org/10.1128/JVI.02438-06
  47. Marcello, T., A. Grakoui, G. Barba-Spaeth, E. S. Machlin, S. V. Kotenko, M. R. MacDonald, and C. M. Rice. 2006. Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131: 1887-1898. https://doi.org/10.1053/j.gastro.2006.09.052
  48. Ank, N., H. West, C. Bartholdy, K. Eriksson, A. R. Thomsen, and S. R. Paludan. 2006. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J. Virol. 80: 4501-4509. https://doi.org/10.1128/JVI.80.9.4501-4509.2006
  49. Ank, N., M. B. Iversen, C. Bartholdy, P. Staeheli, R. Hartmann, U. B. Jensen, F. gnaes-Hansen, A. R. Thomsen, Z. Chen, H. Haugen, K. Klucher, and S. R. Paludan. 2008. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity. J. Immunol. 180: 2474-2485. https://doi.org/10.4049/jimmunol.180.4.2474
  50. Iversen, M. B., N. Ank, J. Melchjorsen, and S. R. Paludan. 2010. Expression of type III interferon (IFN) in the vaginal mucosa is mediated primarily by dendritic cells and displays stronger dependence on NF-kappaB than type I IFNs. J. Virol. 84: 4579-4586. https://doi.org/10.1128/JVI.02591-09
  51. Li, J., S. Hu, L. Zhou, L. Ye, X. Wang, J. Ho, and W. Ho. 2011. Interferon lambda inhibits herpes simplex virus type I infection of human astrocytes and neurons. Glia 59: 58-67. https://doi.org/10.1002/glia.21076
  52. Li, J., L. Ye, X. Wang, S. Hu, and W. Ho. 2012. Induction of interferon-gamma contributes to Toll-like receptor 3-mediated herpes simplex virus type 1 inhibition in astrocytes. J. Neurosci. Res. 90: 399-406. https://doi.org/10.1002/jnr.22758
  53. Ghiasi, H., S. Cai, G. C. Perng, A. B. Nesburn, and S. L. Wechsler. 2000. The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection. Antiviral Res. 45: 33-45. https://doi.org/10.1016/S0166-3542(99)00075-3
  54. Lehmann, C., M. Zeis, and L. Uharek. 2001. Activation of natural killer cells with interleukin 2 (IL-2) and IL-12 increases perforin binding and subsequent lysis of tumour cells. Br. J. Haematol. 114: 660-665. https://doi.org/10.1046/j.1365-2141.2001.02995.x
  55. Ashkar, A. A., and K. L. Rosenthal. 2003. Interleukin-15 and natural killer and NKT cells play a critical role in innate protection against genital herpes simplex virus type 2 infection. J. Virol. 77: 10168-10171. https://doi.org/10.1128/JVI.77.18.10168-10171.2003
  56. Reading, P. C., P. G. Whitney, D. P. Barr, M. Wojtasiak, J. D. Mintern, J. Waithman, and A. G. Brooks. 2007. IL-18, but not IL-12, regulates NK cell activity following intranasal herpes simplex virus type 1 infection. J. Immunol. 179: 3214-3221. https://doi.org/10.4049/jimmunol.179.5.3214
  57. Nandakumar, S., S. N. Woolard, D. Yuan, B. T. Rouse, and U. Kumaraguru. 2008. Natural killer cells as novel helpers in anti-herpes simplex virus immune response. J. Virol. 82: 10820-10831. https://doi.org/10.1128/JVI.00365-08
  58. Staats, H. F., J. E. Oakes, and R. N. Lausch. 1991. Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo $GM1^+$ cells. J. Virol. 65: 6008-6014.
  59. Kassim, S. H., N. K. Rajasagi, X. Zhao, R. Chervenak, and S. R. Jennings. 2006. In vivo ablation of CD11c-positive dendritic cells increases susceptibility to herpes simplex virus type 1 infection and diminishes NK and T-cell responses. J. Virol. 80: 3985-3993. https://doi.org/10.1128/JVI.80.8.3985-3993.2006
  60. Zhao, X., E. Deak, K. Soderberg, M. Linehan, D. Spezzano, J. Zhu, D. M. Knipe, and A. Iwasaki. 2003. Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2. J. Exp. Med. 197: 153-162. https://doi.org/10.1084/jem.20021109
  61. Sato, A., and A. Iwasaki. 2004. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proc. Natl. Acad. Sci. U. S. A 101: 16274-16279. https://doi.org/10.1073/pnas.0406268101
  62. Reske, A., G. Pollara, C. Krummenacher, D. R. Katz, and B. M. Chain. 2008. Glycoprotein-dependent and TLR2-independent innate immune recognition of herpes simplex virus-1 by dendritic cells. J. Immunol. 180: 7525-7536. https://doi.org/10.4049/jimmunol.180.11.7525
  63. Kassim, S. H., N. K. Rajasagi, B. W. Ritz, S. B. Pruett, E. M. Gardner, R. Chervenak, and S. R. Jennings. 2009. Dendritic cells are required for optimal activation of natural killer functions following primary infection with herpes simplex virus type 1. J. Virol. 83: 3175-3186. https://doi.org/10.1128/JVI.01907-08
  64. Frank, G. M., K. A. Buela, D. M. Maker, S. A. Harvey, and R. L. Hendricks. 2012. Early responding dendritic cells direct the local NK response to control herpes simplex virus 1 infection within the cornea. J. Immunol. 188: 1350-1359. https://doi.org/10.4049/jimmunol.1101968
  65. Bryant-Hudson, K. M., and D. J. Carr. 2012. PD-L1-expressing dendritic cells contribute to viral resistance during acute HSV-1 infection. Clin. Dev. Immunol. 2012: 924619.
  66. Lund, J., A. Sato, S. Akira, R. Medzhitov, and A. Iwasaki. 2003. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198: 513-520. https://doi.org/10.1084/jem.20030162
  67. Shen, H., and A. Iwasaki. 2006. A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODNbased vaginal microbicide. J. Clin. Invest. 116: 2237-2243. https://doi.org/10.1172/JCI28681
  68. Lund, J. M., M. M. Linehan, N. Iijima, and A. Iwasaki. 2006. Cutting Edge: Plasmacytoid dendritic cells provide innate immune protection against mucosal viral infection in situ. J. Immunol. 177: 7510-7514. https://doi.org/10.4049/jimmunol.177.11.7510
  69. Mott, K. R., D. Underhill, S. L. Wechsler, T. Town, and H. Ghiasi. 2009. A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages. Virol. J. 6: 56. https://doi.org/10.1186/1743-422X-6-56
  70. Swaminathan, S., X. Hu, X. Zheng, Y. Kriga, J. Shetty, Y. Zhao, R. Stephens, B. Tran, M. W. Baseler, J. Yang, R. A. Lempicki, D. Huang, H. C. Lane, and T. Imamichi. 2013. Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties. Biochem. Biophys. Res. Commun. 434: 228-234. https://doi.org/10.1016/j.bbrc.2013.03.046
  71. Mott, K. R., D. Gate, M. Zandian, S. J. Allen, N. K. Rajasagi, R. N. van, S. Chen, M. Arditi, B. T. Rouse, R. A. Flavell, T. Town, and H. Ghiasi. 2011. Macrophage IL-12p70 signaling prevents HSV-1-induced CNS autoimmunity triggered by autoaggressive $CD4^+$ Tregs. Invest Ophthalmol. Vis. Sci. 52: 2321-2333. https://doi.org/10.1167/iovs.10-6536
  72. Zolini, G. P., G. K. Lima, N. Lucinda, M. A. Silva, M. F. Dias, N. L. Pessoa, B. P. Coura, C. T. Cartelle, R. M. Arantes, E. G. Kroon, and M. A. Campos. 2014. Defense against HSV-1 in a murine model is mediated by iNOS and orchestrated by the activation of TLR2 and TLR9 in trigeminal ganglia. J. Neuroinflammation. 11: 20. https://doi.org/10.1186/1742-2094-11-20
  73. Iijima, N., L. M. Mattei, and A. Iwasaki. 2011. Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue. Proc. Natl. Acad. Sci. U. S. A 108: 284-289. https://doi.org/10.1073/pnas.1005201108
  74. Milligan, G. N. 1999. Neutrophils aid in protection of the vaginal mucosae of immune mice against challenge with herpes simplex virus type 2. J. Virol. 73: 6380-6386.
  75. Molesworth-Kenyon, S. J., N. Popham, A. Milam, J. E. Oakes, and R. N. Lausch. 2012. Resident corneal cells communicate with neutrophils leading to the production of IP-10 during the primary inflammatory response to HSV-1 infection. Int. J. Inflam. 2012: 810359.
  76. Wojtasiak, M., D. L. Pickett, M. D. Tate, S. L. Londrigan, S. Bedoui, A. G. Brooks, and P. C. Reading. 2010. Depletion of $Gr-1^+$, but not $Ly6G^+$, immune cells exacerbates virus replication and disease in an intranasal model of herpes simplex virus type 1 infection. J. Gen. Virol. 91: 2158-2166. https://doi.org/10.1099/vir.0.021915-0
  77. Parr, M. B., and E. L. Parr. 2000. Immunity to vaginal herpes simplex virus-2 infection in B-cell knockout mice. Immunology 101: 126-131. https://doi.org/10.1046/j.1365-2567.2000.00080.x
  78. Gorander, S., A. M. Harandi, M. Lindqvist, T. Bergstrom, and J. A. Liljeqvist. 2012. Glycoprotein G of herpes simplex virus 2 as a novel vaccine antigen for immunity to genital and neurological disease. J. Virol. 86: 7544-7553. https://doi.org/10.1128/JVI.00186-12
  79. Liu, K., D. Jiang, L. Zhang, Z. Yao, Z. Chen, S. Yu, and X. Wang. 2012. Identification of B- and T-cell epitopes from glycoprotein B of herpes simplex virus 2 and evaluation of their immunogenicity and protection efficacy. Vaccine 30: 3034-3041. https://doi.org/10.1016/j.vaccine.2011.10.010
  80. Deshpande, S. P., M. Zheng, M. Daheshia, and B. T. Rouse. 2000. Pathogenesis of herpes simplex virus-induced ocular immunoinflammatory lesions in B-cell-deficient mice. J. Virol. 74: 3517-3524. https://doi.org/10.1128/JVI.74.8.3517-3524.2000
  81. Peek, R., G. M. Verjans, and B. Meek. 2002. Herpes simplex virus infection of the human eye induces a compartmentalized virus-specific B cell response. J. Infect. Dis. 186: 1539-1546. https://doi.org/10.1086/345555
  82. Iijima, N., M. M. Linehan, M. Zamora, D. Butkus, R. Dunn, M. R. Kehry, T. M. Laufer, and A. Iwasaki. 2008. Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. J. Exp. Med. 205: 3041-3052. https://doi.org/10.1084/jem.20082039
  83. Del, C. J., M. Lindqvist, M. Cuello, M. Backstrom, O. Cabrerra, J. Persson, O. Perez, and A. M. Harandi. 2010. Intranasal immunization with a proteoliposome-derived cochleate containing recombinant gD protein confers protective immunity against genital herpes in mice. Vaccine 28: 1193-1200. https://doi.org/10.1016/j.vaccine.2009.11.035
  84. Cortesi, R., L. Ravani, F. Rinaldi, P. Marconi, M. Drechsler, M. Manservigi, R. Argnani, E. Menegatti, E. Esposito, and R. Manservigi. 2013. Intranasal immunization in mice with non-ionic surfactants vesicles containing HSV immunogens: a preliminary study as possible vaccine against genital herpes. Int. J. Pharm. 440: 229-237. https://doi.org/10.1016/j.ijpharm.2012.06.042
  85. Chiuppesi, F., L. Vannucci, L. A. De, M. Lai, B. Matteoli, G. Freer, R. Manservigi, L. Ceccherini-Nelli, F. Maggi, M. Bendinelli, and M. Pistello. 2012. A lentiviral vector-based, herpes simplex virus 1 (HSV-1) glycoprotein B vaccine affords cross-protection against HSV-1 and HSV-2 genital infections. J. Virol. 86: 6563-6574. https://doi.org/10.1128/JVI.00302-12
  86. Kuklin, N. A., M. Daheshia, S. Chun, and B. T. Rouse. 1998. Role of mucosal immunity in herpes simplex virus infection. J. Immunol. 160: 5998-6003.
  87. Dudley, K. L., N. Bourne, and G. N. Milligan. 2000. Immune protection against HSV-2 in B-cell-deficient mice. Virology 270: 454-463. https://doi.org/10.1006/viro.2000.0298
  88. Morrison, L. A., L. Zhu, and L. G. Thebeau. 2001. Vaccineinduced serum immunoglobin contributes to protection from herpes simplex virus type 2 genital infection in the presence of immune T cells. J. Virol. 75: 1195-1204. https://doi.org/10.1128/JVI.75.3.1195-1204.2001
  89. Bettelli, E., T. Korn, M. Oukka, and V. K. Kuchroo. 2008. Induction and effector functions of T(H)17 cells. Nature 453: 1051-1057. https://doi.org/10.1038/nature07036
  90. Suryawanshi, A., T. Veiga-Parga, N. K. Rajasagi, P. B. Reddy, S. Sehrawat, S. Sharma, and B. T. Rouse. 2011. Role of IL-17 and Th17 cells in herpes simplex virus-induced corneal immunopathology. J. Immunol. 187: 1919-1930. https://doi.org/10.4049/jimmunol.1100736
  91. Eo, S. K., S. Lee, S. Chun, and B. T. Rouse. 2001. Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines. J. Virol. 75: 569-578. https://doi.org/10.1128/JVI.75.2.569-578.2001
  92. Kumamoto, Y., L. M. Mattei, S. Sellers, G. W. Payne, and A. Iwasaki. 2011. $CD4^+$ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proc. Natl. Acad. Sci. U. S. A. 108: 8749-8754. https://doi.org/10.1073/pnas.1100567108
  93. Rajasagi, N. K. 2007. The role of $CD4^+$ Helper T cells, IL-2 and IL-15 in the generation of an optimal $CD8^+$ T cell response following infection with herpes simplex virus-1 (HSV-1). Louisiana State University Health Sciences Center-Shreveport, ProQuest, UMI Dissertations Publishing Number: 3311956, p. 56-61.
  94. Ghiasi, H., S. Cai, G. C. Perng, A. B. Nesburn, and S. L. Wechsler. 2000. Both $CD4^+$ and $CD8^+$ T cells are involved in protection against HSV-1 induced corneal scarring. Br. J. Ophthalmol. 84: 408-412. https://doi.org/10.1136/bjo.84.4.408
  95. Koelle, D. M., C. M. Posavad, G. R. Barnum, M. L. Johnson, J. M. Frank, and L. Corey. 1998. Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes. J. Clin. Invest 101: 1500-1508. https://doi.org/10.1172/JCI1758
  96. Coleman, C. A., M. C. Muller-Trutwin, C. Apetrei, and I. Pandrea. 2007. T regulatory cells: aid or hindrance in the clearance of disease? J. Cell Mol. Med. 11: 1291-1325. https://doi.org/10.1111/j.1582-4934.2007.00087.x
  97. Dasgupta, G., A. A. Chentoufi, S. You, P. Falatoonzadeh, L. A. Urbano, A. Akhtarmalik, K. Nguyen, L. Ablabutyan, A. B. Nesburn, and L. BenMohamed. 2011. Engagement of TLR2 reverses the suppressor function of conjunctiva $CD4^+$$CD25^+$ regulatory T cells and promotes herpes simplex virus epitope-specific $CD4^+$$CD25^-$ effector T cell responses. Invest Ophthalmol. Vis. Sci. 52: 3321-3333. https://doi.org/10.1167/iovs.10-6522
  98. Sehrawat, S., S. Suvas, P. P. Sarangi, A. Suryawanshi, and B. T. Rouse. 2008. In vitro-generated antigen-specific $CD4^+$ $CD25^+$ $Foxp3^+$ regulatory T cells control the severity of herpes simplex virus-induced ocular immunoinflammatory lesions. J. Virol. 82: 6838-6851. https://doi.org/10.1128/JVI.00697-08
  99. Kim, J. O., H. R. Cha, E. D. Kim, and M. N. Kweon. 2012. Pathological effect of IL-17A-producing TCRgammadelta(+) T cells in mouse genital mucosa against HSV-2 infection. Immunol. Lett. 147: 34-40. https://doi.org/10.1016/j.imlet.2012.05.006
  100. Jirmo, A. C., C. H. Nagel, C. Bohnen, B. Sodeik, and G. M. Behrens. 2009. Contribution of direct and cross-presentation to CTL immunity against herpes simplex virus 1. J. Immunol. 182: 283-292. https://doi.org/10.4049/jimmunol.182.1.283
  101. St Leger, A. J., B. Peters, J. Sidney, A. Sette, and R. L. Hendricks. 2011. Defining the herpes simplex virus-specific $CD8^+$ T cell repertoire in C57BL/6 mice. J. Immunol. 186: 3927-3933. https://doi.org/10.4049/jimmunol.1003735
  102. van, L. A., M. Ayers, A. G. Brooks, R. M. Coles, W. R. Heath, and F. R. Carbone. 2004. Herpes simplex virus-specific $CD8^+$ T cells can clear established lytic infections from skin and nerves and can partially limit the early spread of virus after cutaneous inoculation. J. Immunol. 172: 392-397. https://doi.org/10.4049/jimmunol.172.1.392
  103. Koelle, D. M., C. M. Posavad, G. R. Barnum, M. L. Johnson, J. M. Frank, and L. Corey. 1998. Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes. J. Clin. Invest 101: 1500-1508. https://doi.org/10.1172/JCI1758
  104. Himmelein, S., A. J. St Leger, J. E. Knickelbein, A. Rowe, M. L. Freeman, and R. L. Hendricks. 2011. Circulating herpes simplex type 1 (HSV-1)-specific $CD8^+$ T cells do not access HSV-1 latently infected trigeminal ganglia. Herpesviridae. 2: 5. https://doi.org/10.1186/2042-4280-2-5
  105. Koelle, D. M., and L. Corey. 2008. Herpes simplex: insights on pathogenesis and possible vaccines. Annu. Rev. Med. 59: 381-395. https://doi.org/10.1146/annurev.med.59.061606.095540
  106. Wilson, S. S., E. Fakioglu, and B. C. Herold. 2009. Novel approaches in fighting herpes simplex virus infections. Expert. Rev. Anti. Infect. Ther. 7: 559-568. https://doi.org/10.1586/eri.09.34
  107. Petrera, E., and C. E. Coto. 2014. Effect of the potent antiviral 1-cinnamoyl-3,11-dihydroxymeliacarpin on cytokine production by murine macrophages stimulated with HSV-2. Phytother. Res. 28: 104-109. https://doi.org/10.1002/ptr.4974
  108. Akira, S., S. Uematsu, and O. Takeuchi. 2006. Pathogen recognition and innate immunity. Cell 124: 783-801. https://doi.org/10.1016/j.cell.2006.02.015
  109. Miller, R. L., M. A. Tomai, C. J. Harrison, and D. I. Bernstein. 2002. Immunomodulation as a treatment strategy for genital herpes: review of the evidence. Int. Immunopharmacol. 2: 443-451. https://doi.org/10.1016/S1567-5769(01)00184-9
  110. Ashkar, A. A., X. D. Yao, N. Gill, D. Sajic, A. J. Patrick, and K. L. Rosenthal. 2004. Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA. J. Infect. Dis. 190: 1841-1849. https://doi.org/10.1086/425079
  111. Boivin, N., Y. Sergerie, S. Rivest, and G. Boivin. 2008. Effect of pretreatment with toll-like receptor agonists in a mouse model of herpes simplex virus type 1 encephalitis. J. Infect. Dis. 198: 664672.
  112. Ashkar, A. A., S. Bauer, W. J. Mitchell, J. Vieira, and K. L. Rosenthal. 2003. Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2. J. Virol. 77: 8948-8956. https://doi.org/10.1128/JVI.77.16.8948-8956.2003
  113. Gill, N., E. J. Davies, and A. A. Ashkar. 2008. The role of toll-like receptor ligands/agonists in protection against genital HSV-2 infection. Am. J. Reprod. Immunol. 59: 35-43.
  114. Sajic, D., A. J. Patrick, and K. L. Rosenthal. 2005. Mucosal delivery of CpG oligodeoxynucleotides expands functional dendritic cells and macrophages in the vagina. Immunology 114: 213-224. https://doi.org/10.1111/j.1365-2567.2004.02081.x
  115. Tumpey, T. M., H. Cheng, X. T. Yan, J. E. Oakes, and R. N. Lausch. 1998. Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-10. J. Leukoc. Biol. 63: 486-492. https://doi.org/10.1002/jlb.63.4.486
  116. Kratholm, S. K., M. B. Iversen, L. Reinert, S. K. Jensen, M. Hokland, T. Andersen, A. Rankin, D. Young, S. Frische, S. R. Paludan, and C. K. Holm. 2013. Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections. PLoS One 8: e81790. https://doi.org/10.1371/journal.pone.0081790
  117. Kim, S. B., Y. W. Han, M. M. Rahman, S. J. Kim, D. J. Yoo, S. H. Kang, K. Kim, and S. K. Eo. 2009. Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with beta2-adrenergic agonist. Exp. Mol. Med. 41: 812-823. https://doi.org/10.3858/emm.2009.41.11.087
  118. Lindqvist, M., J. Persson, K. Thorn, and A. M. Harandi. 2009. The mucosal adjuvant effect of alpha-galactosylceramide for induction of protective immunity to sexually transmitted viral infection. J. Immunol. 182: 6435-6443. https://doi.org/10.4049/jimmunol.0900136
  119. Uyangaa, E., H. K. Lee, and S. K. Eo. 2012. Glutamine and leucine provide enhanced protective immunity against mucosal infection with herpes simplex virus type 1. Immune. Netw. 12: 196-206. https://doi.org/10.4110/in.2012.12.5.196
  120. Kuo, Y. C., Y. C. Lee, Y. L. Leu, W. J. Tsai, and S. C. Chang. 2008. Efficacy of orally administered Lobelia chinensis extracts on herpes simplex virus type 1 infection in BALB/c mice. Antiviral Res. 80: 206-212. https://doi.org/10.1016/j.antiviral.2008.06.009
  121. Cho, A., Y. S. Roh, E. Uyangaa, S. Park, J. W. Kim, K. H. Lim, J. Kwon, S. K. Eo, C. W. Lim, and B. Kim. 2013. Protective effects of red ginseng extract against vaginal herpes simplex virus infection. J. Ginseng. Res. 37: 210-218. https://doi.org/10.5142/jgr.2013.37.210
  122. Petrera, E., and C. E. Coto. 2014. Effect of the potent antiviral 1-cinnamoyl-3,11-dihydroxymeliacarpin on cytokine production by murine macrophages stimulated with HSV-2. Phytother. Res. 28: 104-109. https://doi.org/10.1002/ptr.4974
  123. Ushio, C., H. Ariyasu, T. Ariyasu, S. Arai, T. Ohta, and S. Fukuda. 2009. Suppressive effects of a cyanine dye against herpes simplex virus (HSV)-1 infection. Biomed. Res. 30: 365-368. https://doi.org/10.2220/biomedres.30.365
  124. Balzarini, J., G. Andrei, E. Balestra, D. Huskens, C. Vanpouille, A. Introini, S. Zicari, S. Liekens, R. Snoeck, A. Holy, C. F. Perno, L. Margolis, and D. Schols. 2013. A multi-targeted drug candidate with dual anti-HIV and anti-HSV activity. PLoS Pathog. 9: e1003456. https://doi.org/10.1371/journal.ppat.1003456
  125. Hu, K., X. He, F. Yu, X. Yuan, W. Hu, C. Liu, F. Zhao, and J. Dou. 2011. Immunization with DNA vaccine expressing herpes simplex virus type 1 gD and IL-21 protects against mouse herpes keratitis. Immunol. Invest 40: 265-278.
  126. Awasthi, S., J. W. Balliet, J. A. Flynn, J. M. Lubinski, C. E. Shaw, D. J. DiStefano, M. Cai, M. Brown, J. F. Smith, R. Kowalski, R. Swoyer, J. Galli, V. Copeland, S. Rios, R. C. Davidson, M. Salnikova, S. Kingsley, J. Bryan, D. R. Casimiro, and H. M. Friedman. 2014. Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs. J. Virol. 88: 2000-2010. https://doi.org/10.1128/JVI.03163-13
  127. Brans, R., and F. Yao. 2010. Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV) type 1 protects against HSV-2 genital disease in guinea pigs. BMC. Microbiol. 10: 163. https://doi.org/10.1186/1471-2180-10-163
  128. Koelle, D. M., A. Magaret, C. L. McClurkan, M. L. Remington, T. Warren, F. Teofilovici, and A. Wald. 2008. Phase I dose-escalation study of a monovalent heat shock protein 70-herpes simplex virus type 2 (HSV-2) peptide-based vaccine designed to prime or boost CD8 T-cell responses in HSV-naive and HSV-2-infected subjects. Clin. Vaccine Immunol. 15: 773-782. https://doi.org/10.1128/CVI.00020-08
  129. Zhang, X., A. A. Chentoufi, G. Dasgupta, A. B. Nesburn, M. Wu, X. Zhu, D. Carpenter, S. L. Wechsler, S. You, and L. BenMohamed. 2009. A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic $CD8^+$ T cells and protects against herpes simplex virus type 2 challenge. Mucosal. Immunol. 2: 129143.
  130. Jamali, A., M. H. Roostaee, H. Soleimanjahi, P. F. Ghaderi, and T. Bamdad. 2007. DNA vaccine-encoded glycoprotein B of HSV-1 fails to protect chronic morphine-treated mice against HSV-1 challenge. Comp Immunol. Microbiol. Infect. Dis. 30: 71-80. https://doi.org/10.1016/j.cimid.2006.10.002
  131. Johnston, C., D. M. Koelle, and A. Wald. 2011. HSV-2: in pursuit of a vaccine. J. Clin. Invest 121: 4600-4609. https://doi.org/10.1172/JCI57148
  132. Belshe, R. B., P. A. Leone, D. I. Bernstein, A. Wald, M. J. Levin, J. T. Stapleton, I. Gorfinkel, R. L. Morrow, M. G. Ewell, A. Stokes-Riner, G. Dubin, T. C. Heineman, J. M. Schulte, and C. D. Deal. 2012. Efficacy results of a trial of a herpes simplex vaccine. N. Engl. J. Med. 366: 3443.
  133. Stanberry, L. R., D. I. Bernstein, R. L. Burke, C. Pachl, and M. G. Myers. 1987. Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes. J. Infect. Dis. 155: 914-920. https://doi.org/10.1093/infdis/155.5.914
  134. Bourne, N., F. J. Bravo, M. Francotte, D. I. Bernstein, M. G. Myers, M. Slaoui, and L. R. Stanberry. 2003. Herpes simplex virus (HSV) type 2 glycoprotein D subunit vaccines and protection against genital HSV-1 or HSV-2 disease in guinea pigs. J. Infect. Dis. 187: 542-549. https://doi.org/10.1086/374002
  135. Bourne, N., G. N. Milligan, L. R. Stanberry, R. Stegall, and R. B. Pyles. 2005. Impact of immunization with glycoprotein D2/AS04 on herpes simplex virus type 2 shedding into the genital tract in guinea pigs that become infected. J. Infect. Dis. 192: 2117-2123. https://doi.org/10.1086/498247
  136. Stanberry, L. R., S. L. Spruance, A. L. Cunningham, D. I. Bernstein, A. Mindel, S. Sacks, S. Tyring, F. Y. Aoki, M. Slaoui, M. Denis, P. Vandepapeliere, and G. Dubin. 2002. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N. Engl. J. Med. 347: 1652-1661. https://doi.org/10.1056/NEJMoa011915
  137. Corey, L., A. G. Langenberg, R. Ashley, R. E. Sekulovich, A. E. Izu, J. M. Douglas, Jr., H. H. Handsfield, T. Warren, L. Marr, S. Tyring, R. DiCarlo, A. A. Adimora, P. Leone, C. L. Dekker, R. L. Burke, W. P. Leong, and S. E. Straus. 1999. Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group. JAMA 282: 331-340.
  138. Ghasemi, M., M. Erturk, K. Buruk, and M. Sonmez. 2013. Induction of potent protection against acute and latent herpes simplex virus infection in mice vaccinated with dendritic cells. Cytotherapy 15: 352-361. https://doi.org/10.1016/j.jcyt.2012.11.012

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