1887

Journal of General Virology header logo

Volume 98, Issue 10

A lethal model of disseminated dengue virus type 1 infection in AG129 mice Free

Abstract

The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): AG129 mouse , dengue virus , Flavivirus , mouse model and pathogenicity
© 2017 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000923
2017-10-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/10/2507.html?itemId=/content/journal/jgv/10.1099/jgv.0.000923&mimeType=html&fmt=ahah

References

  1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW et al. The global distribution and burden of dengue. Nature 2013; 496:504–507 [View Article][PubMed]
     [Google Scholar]
  2. Shepard DS, Undurraga EA, Halasa YA, Stanaway JD. The global economic burden of dengue: a systematic analysis. Lancet Infect Dis 2016; 16:935–941 [View Article][PubMed]
     [Google Scholar]
  3. Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis 2012; 6:e1760 [View Article][PubMed]
     [Google Scholar]
  4. Messina JP, Brady OJ, Scott TW, Zou C, Pigott DM et al. Global spread of dengue virus types: mapping the 70 year history. Trends Microbiol 2014; 22:138–146 [View Article][PubMed]
     [Google Scholar]
  5. Kraemer MU, Sinka ME, Duda KA, Mylne AQ, Shearer FM et al. The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus . Elife 2015; 4:e08347 [View Article][PubMed]
     [Google Scholar]
  6. World Health Organization Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control 2009 p. 147
     [Google Scholar]
  7. Cassetti MC, Halstead SB. Consultation on dengue vaccines: progress in understanding protection, 26–28 June 2013, Rockville, Maryland. Vaccine 2014; 32:3115–3121 [View Article]
     [Google Scholar]
  8. Guzman MG, Alvarez M, Halstead SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol 2013; 158:1445–1459 [View Article][PubMed]
     [Google Scholar]
  9. Rothman AL. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 2011; 11:532–543 [View Article][PubMed]
     [Google Scholar]
  10. Hadinegoro SR, Arredondo-García JL, Capeding MR, Deseda C, Chotpitayasunondh T et al. Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. N Engl J Med 2015; 373:1195–1206 [View Article][PubMed]
     [Google Scholar]
  11. Villar L, Dayan GH, Arredondo-García JL, Rivera DM, Cunha R et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med 2015; 372:113–123 [View Article][PubMed]
     [Google Scholar]
  12. WHO Dengue vaccine: WHO position paper – July 2016. Wkly Epidemiol Rec 20162016; 91:349–364
     [Google Scholar]
  13. Chan KW, Watanabe S, Kavishna R, Alonso S, Vasudevan SG. Animal models for studying dengue pathogenesis and therapy. Antiviral Res 2015; 123:5–14 [View Article][PubMed]
     [Google Scholar]
  14. Sarathy VV, Milligan GN, Bourne N, Barrett AD. Mouse models of dengue virus infection for vaccine testing. Vaccine 2015; 33:7051–7060 [View Article][PubMed]
     [Google Scholar]
  15. Johnson AJ, Roehrig JT. New mouse model for dengue virus vaccine testing. J Virol 1999; 73:783–786[PubMed]
     [Google Scholar]
  16. Shresta S, Sharar KL, Prigozhin DM, Beatty PR, Harris E. Murine model for dengue virus-induced lethal disease with increased vascular permeability. J Virol 2006; 80:10208–10217 [View Article][PubMed]
     [Google Scholar]
  17. Zellweger RM, Prestwood TR, Shresta S. Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe 2010; 7:128–139 [View Article][PubMed]
     [Google Scholar]
  18. Tan GK, Ng JK, Trasti SL, Schul W, Yip G et al. A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice. PLoS Negl Trop Dis 2010; 4:e672 [View Article][PubMed]
     [Google Scholar]
  19. Tan GK, Ng JK, Lim AH, Yeo KP, Angeli V et al. Subcutaneous infection with non-mouse adapted Dengue virus D2Y98P strain induces systemic vascular leakage in AG129 mice. Ann Acad Med Singapore 2011; 40:523–532[PubMed]
     [Google Scholar]
  20. Sarathy VV, White M, Li L, Gorder SR, Pyles RB et al. A lethal murine infection model for dengue virus 3 in AG129 mice deficient in type I and II interferon receptors leads to systemic disease. J Virol 2015; 89:1254–1266 [View Article][PubMed]
     [Google Scholar]
  21. Milligan GN, Sarathy VV, Infante E, Li L, Campbell GA et al. A Dengue virus type 4 model of disseminated lethal infection in AG129 mice. PLoS One 2015; 10:e0125476 [View Article][PubMed]
     [Google Scholar]
  22. Sarathy VV, Infante E, Li L, Campbell GA, Wang T et al. Characterization of lethal dengue virus type 4 (DENV-4) TVP-376 infection in mice lacking both IFN-α/β and IFN-γ receptors (AG129) and comparison with the DENV-2 AG129 mouse model. J Gen Virol 2015; 96:3035–3048 [View Article][PubMed]
     [Google Scholar]
  23. Repik PM, Dalrymple JM, Brandt WE, Mccown JM, Russell PK. RNA fingerprinting as a method for distinguishing dengue 1 virus strains. Am J Trop Med Hyg 1983; 32:577–589 [View Article][PubMed]
     [Google Scholar]
  24. Watanabe S, Chan KW, Dow G, Ooi EE, Low JG et al. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy. Antiviral Res 2016; 127:10–19 [View Article][PubMed]
     [Google Scholar]
  25. Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med 2012; 366:1423–1432 [View Article][PubMed]
     [Google Scholar]
  26. Nguyen MT, Ho TN, Nguyen VV, Nguyen TH, Ha MT et al. An evidence-based algorithm for early prognosis of severe dengue in the outpatient setting. Clin Infect Dis 2017; 64:656–663 [View Article][PubMed]
     [Google Scholar]
  27. Vakrani GP, Subramanyam NT. Acute renal failure in dengue infection. J Clin Diagn Res 2017; 11:OC10–OC3 [View Article][PubMed]
     [Google Scholar]
  28. Rathakrishnan A, Wang SM, Hu Y, Khan AM, Ponnampalavanar S et al. Cytokine expression profile of dengue patients at different phases of illness. PLoS One 2012; 7:e52215 [View Article][PubMed]
     [Google Scholar]
  29. Lee YH, Leong WY, Wilder-Smith A. Markers of dengue severity: a systematic review of cytokines and chemokines. J Gen Virol 2016; 97:3103–3119 [View Article][PubMed]
     [Google Scholar]
  30. Balsitis SJ, Williams KL, Lachica R, Flores D, Kyle JL et al. Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. PLoS Pathog 2010; 6:e1000790 [View Article][PubMed]
     [Google Scholar]
  31. Orozco S, Schmid MA, Parameswaran P, Lachica R, Henn MR et al. Characterization of a model of lethal dengue virus 2 infection in C57BL/6 mice deficient in the alpha/beta interferon receptor. J Gen Virol 2012; 93:2152–2157 [View Article][PubMed]
     [Google Scholar]
  32. Kanesa-Thasan N, Sun W, Kim-Ahn G, van Albert S, Putnak JR et al. Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers. Vaccine 2001; 19:3179–3188 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000923
Loading
A lethal model of disseminated dengue virus type 1 infection in AG129 mice
J. Gen. Virol. 98, 2507 (2017); https://doi.org/10.1099/jgv.0.000923
/content/journal/jgv/10.1099/jgv.0.000923
/content/journal/jgv/10.1099/jgv.0.000923
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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