1887

Abstract

The host and viral factors that influence disease outcome during flavivirus infections are not fully understood. Using the live attenuated yellow fever virus (YFV) vaccine strain 17D as a model system we evaluated how viral dose, inoculation route and immunopathogenesis contributed to disease outcome in mice deficient in the type I IFN response. We found that YFV-17D infection of IFN-α/β receptor knockout mice resulted in three distinct disease outcomes: no clinical signs of disease, fatal viscerotropic disease or fatal neurotropic disease. Interestingly, viral load at disease onset did not correlate with disease outcome. However, we found increased immune infiltrates in the brain tissues of mice that developed neurotropic disease. Additionally, mice that developed viscerotropic disease, as characterized by liver and spleen pathology and/or intestinal haemorrhage, had significantly elevated levels of alanine aminotransferase, monocyte chemotactic protein and IFN-inducible protein (IP)-10 as compared with mice with no clinical signs of disease or neurotropic disease. Furthermore, mice treated with recombinant IP-10 throughout YFV-17D infection showed increased mortality and an increased percentage of mice with viscerotropic disease. Our results demonstrated that viral load did not correlate with pathogenesis, and the host immune response played a pivotal role in disease outcome and contributed to YFV-17D pathogenesis in mice.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000075
2015-06-01
2019-10-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/6/1328.html?itemId=/content/journal/jgv/10.1099/vir.0.000075&mimeType=html&fmt=ahah

References

  1. Anonymous. ( 1966; ). Fatal viral encephalitis following 17D yellow fever vaccine inoculation. Report of a case in a 3-year-old child. . JAMA 198:, 671–672. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bae H.-G., Domingo C., Tenorio A., de Ory F., Muñoz J., Weber P., Teuwen D. E., Niedrig M.. ( 2008; ). Immune response during adverse events after 17D-derived yellow fever vaccination in Europe. . J Infect Dis 197:, 1577–1584. [CrossRef] [PubMed]
    [Google Scholar]
  3. Barrett A. D., Gould E. A.. ( 1986; ). Comparison of neurovirulence of different strains of yellow fever virus in mice. . J Gen Virol 67:, 631–637. [CrossRef] [PubMed]
    [Google Scholar]
  4. Beck A., Tesh R. B., Wood T. G., Widen S. G., Ryman K. D., Barrett A. D.. ( 2014; ). Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing. . J Infect Dis 209:, 334–344. [CrossRef] [PubMed]
    [Google Scholar]
  5. Belsher J. L., Gay P., Brinton M., DellaValla J., Ridenour R., Lanciotti R., Perelygin A., Zaki S., Paddock C. et al. ( 2007; ). Fatal multiorgan failure due to yellow fever vaccine-associated viscerotropic disease. . Vaccine 25:, 8480–8485. [CrossRef] [PubMed]
    [Google Scholar]
  6. Brown A. N., Kent K. A., Bennett C. J., Bernard K. A.. ( 2007; ). Tissue tropism and neuroinvasion of West Nile virus do not differ for two mouse strains with different survival rates. . Virology 368:, 422–430. [CrossRef] [PubMed]
    [Google Scholar]
  7. Card J. P., Whealy M. E., Robbins A. K., Moore R. Y., Enquist L. W.. ( 1991; ). Two alpha-herpesvirus strains are transported differentially in the rodent visual system. . Neuron 6:, 957–969. [CrossRef] [PubMed]
    [Google Scholar]
  8. Centers for Disease Control and Prevention ( 2002; ). Adverse events associated with 17D-derived yellow fever vaccination – United States, 2001–2002. . MMWR Morb Mortal Wkly Rep 51:, 989–993.[PubMed]
    [Google Scholar]
  9. Cetron M. S., Marfin A. A., Julian K. G., Gubler D. J., Sharp D. J., Barwick R. S., Weld L. H., Chen R., Clover R. D. et al. ( 2002; ). Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. . MMWR Recomm Rep 51: (RR-17), 1–11.[PubMed]
    [Google Scholar]
  10. Chan R. C., Penney D. J., Little D., Carter I. W., Roberts J. A., Rawlinson W. D.. ( 2001; ). Hepatitis and death following vaccination with 17D-204 yellow fever vaccine. . Lancet 358:, 121–122. [CrossRef] [PubMed]
    [Google Scholar]
  11. Chen H. W., King K., Tu J., Sanchez M., Luster A. D., Shresta S.. ( 2013; ). The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus. . J Immunol 191:, 4194–4201. [CrossRef] [PubMed]
    [Google Scholar]
  12. Dominguez A., Baruch E.. ( 1963; ). Histopathology of the central nervous system in Swiss mice intracerebrally inoculated with 17-D strain of yellow fever virus. . Am J Trop Med Hyg 12:, 815–819.[PubMed]
    [Google Scholar]
  13. Erickson A. K., Pfeiffer J. K.. ( 2013; ). Dynamic viral dissemination in mice infected with yellow fever virus strain 17D. . J Virol 87:, 12392–12397. [CrossRef] [PubMed]
    [Google Scholar]
  14. Fink J., Gu F., Ling L., Tolfvenstam T., Olfat F., Chin K. C., Aw P., George J., Kuznetsov V. A. et al. ( 2007; ). Host gene expression profiling of dengue virus infection in cell lines and patients. . PLoS Negl Trop Dis 1:, e86. [CrossRef] [PubMed]
    [Google Scholar]
  15. Fitzgeorge R., Bradish C. J.. ( 1980; ). The in vivo differentiation of strains of yellow fever virus in mice. . J Gen Virol 46:, 1–13. [CrossRef] [PubMed]
    [Google Scholar]
  16. Fox J. P.. ( 1943; ). Immunity to yellow fever encephalitis of monkeys and mice immunized by neural and extraneural routes. . J Exp Med 77:, 487–506. [CrossRef] [PubMed]
    [Google Scholar]
  17. Gerasimon G., Lowry K.. ( 2005; ). Rare case of fatal yellow fever vaccine-associated viscerotropic disease. . South Med J 98:, 653–656. [CrossRef] [PubMed]
    [Google Scholar]
  18. Goodman G. T., Koprowski H.. ( 1962; ). Macrophages as a cellular expression of inherited natural resistance. . Proc Natl Acad Sci U S A 48:, 160–165. [CrossRef] [PubMed]
    [Google Scholar]
  19. Guirakhoo F., Kitchener S., Morrison D., Forrat R., McCarthy K., Nichols R., Yoksan S., Duan X., Ermak T. H. et al. ( 2006; ). Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax-DEN2) vaccine: Phase I clinical trial for safety and immunogenicity: effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes. . Hum Vaccin 2:, 60–67. [CrossRef] [PubMed]
    [Google Scholar]
  20. Guy B., Guirakhoo F., Barban V., Higgs S., Monath T. P., Lang J.. ( 2010; ). Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses. . Vaccine 28:, 632–649. [CrossRef] [PubMed]
    [Google Scholar]
  21. Hahn C. S., Dalrymple J. M., Strauss J. H., Rice C. M.. ( 1987; ). Comparison of the virulent Asibi strain of yellow fever virus with the 17D vaccine strain derived from it. . Proc Natl Acad Sci U S A 84:, 2019–2023. [CrossRef] [PubMed]
    [Google Scholar]
  22. Hase T., Dubois D. R., Summers P. L.. ( 1990; ). Comparative study of mouse brains infected with Japanese encephalitis virus by intracerebral or intraperitoneal inoculation. . Int J Exp Pathol 71:, 857–869.[PubMed]
    [Google Scholar]
  23. Horsfall F. L., Tam I.. (editors) ( 1965; ). Viral and Rickettsial Infections of Man, , 4th edn.. Philadelphia, PA:: Lippincott;.
    [Google Scholar]
  24. Hsieh M. F., Lai S. L., Chen J. P., Sung J. M., Lin Y. L., Wu-Hsieh B. A., Gerard C., Luster A., Liao F.. ( 2006; ). Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. . J Immunol 177:, 1855–1863. [CrossRef] [PubMed]
    [Google Scholar]
  25. Ida-Hosonuma M., Iwasaki T., Yoshikawa T., Nagata N., Sato Y., Sata T., Yoneyama M., Fujita T., Taya C. et al. ( 2005; ). The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus. . J Virol 79:, 4460–4469. [CrossRef] [PubMed]
    [Google Scholar]
  26. Kengsakul K., Sathirapongsasuti K., Punyagupta S.. ( 2002; ). Fatal myeloencephalitis following yellow fever vaccination in a case with HIV infection. . J Med Assoc Thai 85:, 131–134.[PubMed]
    [Google Scholar]
  27. Khaiboullina S. F., Rizvanov A. A., Holbrook M. R., St Jeor S.. ( 2005; ). Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression. . Virology 342:, 167–176. [CrossRef] [PubMed]
    [Google Scholar]
  28. Klein R. S., Lin E., Zhang B., Luster A. D., Tollett J., Samuel M. A., Engle M., Diamond M. S.. ( 2005; ). Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis. . J Virol 79:, 11457–11466. [CrossRef] [PubMed]
    [Google Scholar]
  29. Kumar M., Roe K., Orillo B., Muruve D. A., Nerurkar V. R., Gale M. Jr, Verma S.. ( 2013; ). Inflammasome adaptor protein Apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in West Nile virus encephalitis. . J Virol 87:, 3655–3667. [CrossRef] [PubMed]
    [Google Scholar]
  30. Lee E., Lobigs M.. ( 2008; ). E protein domain III determinants of yellow fever virus 17D vaccine strain enhance binding to glycosaminoglycans, impede virus spread, and attenuate virulence. . J Virol 82:, 6024–6033. [CrossRef] [PubMed]
    [Google Scholar]
  31. Lee E., Wright P. J., Davidson A., Lobigs M.. ( 2006; a). Virulence attenuation of Dengue virus due to augmented glycosaminoglycan-binding affinity and restriction in extraneural dissemination. . J Gen Virol 87:, 2791–2801. [CrossRef] [PubMed]
    [Google Scholar]
  32. Lee Y. R., Liu M. T., Lei H. Y., Liu C. C., Wu J. M., Tung Y. C., Lin Y. S., Yeh T. M., Chen S. H., Liu H. S.. ( 2006; b). MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells. . J Gen Virol 87:, 3623–3630. [CrossRef] [PubMed]
    [Google Scholar]
  33. Liprandi F., Walder R.. ( 1983; ). Replication of virulent and attenuated strains of yellow fever virus in human monocytes and macrophage-like cells (U937). . Arch Virol 76:, 51–61. [CrossRef] [PubMed]
    [Google Scholar]
  34. Liu T., Chambers T. J.. ( 2001; ). Yellow fever virus encephalitis: properties of the brain-associated T-cell response during virus clearance in normal and gamma interferon-deficient mice and requirement for CD4+ lymphocytes. . J Virol 75:, 2107–2118. [CrossRef] [PubMed]
    [Google Scholar]
  35. Liu M., Guo S., Hibbert J. M., Jain V., Singh N., Wilson N. O., Stiles J. K.. ( 2011; ). CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. . Cytokine Growth Factor Rev 22:, 121–130.[PubMed]
    [Google Scholar]
  36. Martin M., Tsai T. F., Cropp B., Chang G. J., Holmes D. A., Tseng J., Shieh W., Zaki S. R., Al-Sanouri I. et al. ( 2001; ). Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases. . Lancet 358:, 98–104. [CrossRef] [PubMed]
    [Google Scholar]
  37. Mateo R. I., Xiao S. Y., Travassos da Rosa A. P., Lei H., Guzman H., Lu L., Tesh R. B.. ( 2007; ). Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters. . Am J Trop Med Hyg 77:, 919–924.[PubMed]
    [Google Scholar]
  38. Meier K. C., Gardner C. L., Khoretonenko M. V., Klimstra W. B., Ryman K. D.. ( 2009; ). A mouse model for studying viscerotropic disease caused by yellow fever virus infection. . PLoS Pathog 5:, e1000614. [CrossRef] [PubMed]
    [Google Scholar]
  39. Monath T. P.. ( 2008; ). Treatment of yellow fever. . Antiviral Res 78:, 116–124. [CrossRef] [PubMed]
    [Google Scholar]
  40. Monath T. P., Barrett A. D.. ( 2003; ). Pathogenesis and pathophysiology of yellow fever. . Adv Virus Res 60:, 343–395. [CrossRef] [PubMed]
    [Google Scholar]
  41. Monath T. P., Guirakhoo F., Nichols R., Yoksan S., Schrader R., Murphy C., Blum P., Woodward S., McCarthy K. et al. ( 2003; ). Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen. . J Infect Dis 188:, 1213–1230. [CrossRef] [PubMed]
    [Google Scholar]
  42. Monath T. P., Liu J., Kanesa-Thasan N., Myers G. A., Nichols R., Deary A., McCarthy K., Johnson C., Ermak T. et al. ( 2006; ). A live, attenuated recombinant West Nile virus vaccine. . Proc Natl Acad Sci U S A 103:, 6694–6699. [CrossRef] [PubMed]
    [Google Scholar]
  43. Monath T. P., Gershman M., Staples J. E., Barrett A. D.. ( 2013; ). Yellow fever vaccine. . In Vaccines, , 6th edn., pp. 870–968. Edited by Plotkin S. A., Orenstein W., Offit P. A... London:: Saunders;.
    [Google Scholar]
  44. Ohka S., Yang W. X., Terada E., Iwasaki K., Nomoto A.. ( 1998; ). Retrograde transport of intact poliovirus through the axon via the fast transport system. . Virology 250:, 67–75. [CrossRef] [PubMed]
    [Google Scholar]
  45. Paessler S., Walker D. H.. ( 2013; ). Pathogenesis of the viral hemorrhagic fevers. . Annu Rev Pathol 8:, 411–440. [CrossRef] [PubMed]
    [Google Scholar]
  46. Prestwood T. R., Prigozhin D. M., Sharar K. L., Zellweger R. M., Shresta S.. ( 2008; ). A mouse-passaged dengue virus strain with reduced affinity for heparan sulfate causes severe disease in mice by establishing increased systemic viral loads. . J Virol 82:, 8411–8421. [CrossRef] [PubMed]
    [Google Scholar]
  47. Pugachev K. V., Guirakhoo F., Monath T. P.. ( 2005; ). New developments in flavivirus vaccines with special attention to yellow fever. . Curr Opin Infect Dis 18:, 387–394. [CrossRef] [PubMed]
    [Google Scholar]
  48. Querec T. D., Akondy R. S., Lee E. K., Cao W., Nakaya H. I., Teuwen D., Pirani A., Gernert K., Deng J. et al. ( 2009; ). Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. . Nat Immunol 10:, 116–125. [CrossRef] [PubMed]
    [Google Scholar]
  49. Rathakrishnan A., Wang S. M., Hu Y., Khan A. M., Ponnampalavanar S., Lum L. C., Manikam R., Sekaran S. D.. ( 2012; ). Cytokine expression profile of dengue patients at different phases of illness. . PLoS One 7:, e52215. [CrossRef] [PubMed]
    [Google Scholar]
  50. Samuel M. A., Wang H., Siddharthan V., Morrey J. D., Diamond M. S.. ( 2007; ). Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. . Proc Natl Acad Sci U S A 104:, 17140–17145. [CrossRef] [PubMed]
    [Google Scholar]
  51. Schlesinger J. J., Brandriss M. W.. ( 1981; ). Antibody-mediated infection of macrophages and macrophage-like cell lines with 17D-yellow fever virus. . J Med Virol 8:, 103–117. [CrossRef] [PubMed]
    [Google Scholar]
  52. Sellards A. W.. ( 1931; ). The behavior of the virus of yellow fever in monkeys and mice. . Proc Natl Acad Sci U S A 17:, 339–343. [CrossRef] [PubMed]
    [Google Scholar]
  53. Shehan D. C. H., Barbara B.. ( 1980; ). Theory and Practice of Histotechnology, , 2nd edn.. Columbus, OH:: Battelle Press;.
    [Google Scholar]
  54. Shirato K., Kimura T., Mizutani T., Kariwa H., Takashima I.. ( 2004; ). Different chemokine expression in lethal and non-lethal murine West Nile virus infection. . J Med Virol 74:, 507–513. [CrossRef] [PubMed]
    [Google Scholar]
  55. Silva M. L., Espírito-Santo L. R., Martins M. A., Silveira-Lemos D., Peruhype-Magalhães V., Caminha R. C., de Andrade Maranhão-Filho P., Auxiliadora-Martins M., de Menezes Martins R. et al. ( 2010; ). Clinical and immunological insights on severe, adverse neurotropic and viscerotropic disease following 17D yellow fever vaccination. . Clin Vaccine Immunol 17:, 118–126. [CrossRef] [PubMed]
    [Google Scholar]
  56. Sung J. M., Lee C. K., Wu-Hsieh B. A.. ( 2012; ). Intrahepatic infiltrating NK and CD8 T cells cause liver cell death in different phases of dengue virus infection. . PLoS One 7:, e46292. [CrossRef] [PubMed]
    [Google Scholar]
  57. ter Meulen J., Sakho M., Koulemou K., Magassouba N., Bah A., Preiser W., Daffis S., Klewitz C., Bae H. G. et al. ( 2004; ). Activation of the cytokine network and unfavorable outcome in patients with yellow fever. . J Infect Dis 190:, 1821–1827. [CrossRef] [PubMed]
    [Google Scholar]
  58. Theiler M.. ( 1930; ). Susceptibility of white mice to the virus of yellow fever. . Science 71:, 367. [CrossRef] [PubMed]
    [Google Scholar]
  59. Thibodeaux B. A., Garbino N. C., Liss N. M., Piper J., Blair C. D., Roehrig J. T.. ( 2012; ). A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain. . Vaccine 30:, 3180–3187. [CrossRef] [PubMed]
    [Google Scholar]
  60. Tyler K. L., McPhee D. A., Fields B. N.. ( 1986; ). Distinct pathways of viral spread in the host determined by reovirus S1 gene segment. . Science 233:, 770–774. [CrossRef] [PubMed]
    [Google Scholar]
  61. Vasconcelos P. F., Luna E. J., Galler R., Silva L. J., Coimbra T. L., Barros V. L., Monath T. P., Rodigues S. G., Laval C. et al. ( 2001; ). Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. . Lancet 358:, 91–97. [CrossRef] [PubMed]
    [Google Scholar]
  62. Wang T., Town T., Alexopoulou L., Anderson J. F., Fikrig E., Flavell R. A.. ( 2004; ). Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. . Nat Med 10:, 1366–1373. [CrossRef] [PubMed]
    [Google Scholar]
  63. Wang P. Z., Li Z. D., Yu H. T., Zhang Y., Wang W., Jiang W., Bai X. F.. ( 2012; ). Elevated serum concentrations of inflammatory cytokines and chemokines in patients with haemorrhagic fever with renal syndrome. . J Int Med Res 40:, 648–656. [CrossRef] [PubMed]
    [Google Scholar]
  64. Wauquier N., Becquart P., Padilla C., Baize S., Leroy E. M.. ( 2010; ). Human fatal Zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. . PLoS Negl Trop Dis 4:, e837. [CrossRef] [PubMed]
    [Google Scholar]
  65. Woods A.E., Roy C.. ( 1996; ). Laboratory Histopathology: A Complete Reference. London:: Churchill Livingston;.
    [Google Scholar]
  66. Zisman B., Wheelock E. F., Allison A. C.. ( 1971; ). Role of macrophages and antibody in resistance of mice against yellow fever virus. . J Immunol 107:, 236–243.[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000075
Loading
/content/journal/jgv/10.1099/vir.0.000075
Loading

Data & Media loading...

Supplements

Supplementary Data



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error