skip to main content

BALB/c Mice as Animal Model in Dengue Infection Research: Role of Endothelial Activation

1Tropic and Infectious disease division, Internal medicine dept, Faculty of Medicine, Universitas Udayana, Indonesia

2Prof. I.G.N.G.Ngoerah hospital, Indonesia

3Hematology and Oncology division, Internal medicine dept, Faculty of Medicine, Universitas Udayana, Indonesia

4 Farmacology dept, Faculty of Medicine, Universitas Udayana, Indonesia

View all affiliations
Received: 21 Feb 2023; Revised: 12 Jun 2023; Accepted: 21 Jun 2023; Available online: 31 Aug 2023; Published: 31 Aug 2023.
Open Access Copyright (c) 2023 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Citation Format:

Introduction. There were various challenges in using experimental animals model for dengue infection studies aside from the fact that dengue infection only naturally affects humans and does not manifest clinical signs as in humans. Various experimental animals have been used in dengue research, but the mouse model is more widely used since it is easier to obtain although sometimes they do not show clinical symptoms but may still measure the immune response. BALB/c mice are immunocompetent mice that have the potential to be used in dengue infection research. Endothelial cell activation plays a role in the pathogenesis of dengue virus infection which contributes to plasma leakage. One of the biomarkers of endothelial cell activation is soluble intercellular adhesion molecule 1 (sICAM-1).

Method. An analytic observational study was conducted using BALB/c mice aged 8 weeks and weighed 40 grams. Selected BALB/c mice were randomly assigned to serotype 2 dengue virus containing 2.1 x 106 pfu/ml intraperitoneally, given only once. A total of 11 mice were injected with dengue virus serotype 2 and 11 mice were not injected with dengue virus. On the second day of virus injection, non structural (NS) 1 antigen dengue examination was carried out to prove that the BALB/c mice were indeed infected with dengue virus. In BALB/c mice that were proven to be infected with dengue virus, sICAM-1 levels were examined in serum after 7 days of infection. Mice that were not injected with dengue virus also examined sICAM-1

Results. All of BALB/c mice injected with dengue virus were proven to be infected, as indicated by the detection of NS1 antigen in their serum. The mean serum level of NS1 antigen was 88.35 ng/ml (mean 95.34 ng/ml and standard deviation 21.94). The level of sICAM-1 in BALB/c mice infected with dengue virus (mean = 1.34) was significantly higher than mice that were not infected (mean =  0.79), with a p-value 0.045

Conclusions. BALB/c mice were proven to be infected with dengue virus by detecting ns1 dengue virus antigen in the serum. The sICAM-1 levels in the group of BALB/c mice infected with dengue serotype 2 were significantly higher than the BALB/c mice that were not infected with dengue virus.

Fulltext View|Download
Keywords: BALB/c mice; ns1 antigen dengue; sICAM-1

Article Metrics:

  1. World Health Organization, 2011. Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. Revised and expanded edition
  2. Gubler, D.J. 1998. Dengue and Dengue Hemorrhagic Fever. Clinical Microbiology Reviews, 11:480-496
  3. Srikiatkhachorn, A., Kelley, J.F. 2014. Endothelial Cells in Dengue Hemorrhagic Fever. Antiviral Res, 0: 160-170
  4. Dalrymple, N.A., Mackow, E.R. 2012. Roles for Endothelial Cells in Dengue Virus Infection. Advances in Virology, Article ID 840654 doi: 10.1155/2012/840654
  5. Zompi, S., Harris, E. 2012. Animal Models of dengue Virus Infection. Viruses, 4: 62-82
  6. Chan, K.W.K., Watanabe, S., Kavishna, R., Alonso, S. 2015. Animal model for studying dengue pathogenesis and therapy. Antiviral Research, 123: 5-14
  7. Huang, K.J., Li, S.Y., Chen, S.C., Liu, H.S., Lin, Y.S., Yeh, T.M., Liu, C.C., Lei,
  8. H.Y. 2000. Manifestation of thrombocytopenia in dengue-2-virus infected- mice. Journal of General Virology, 81: 2127-2182
  9. Paes, M.V., Pinhao, A.T., Barreto, D.F., Costa, S.M., Olievera, M.P., Nogueira,
  10. A.C., Takiya, C.M., Farias-Filho, J.C., Schatzmayr, H.G., Alves, A.M., Barth,
  11. O.M. 2005. Liver Injury and viremia in mice infected with dengue-2 virus. Virology, 338: 236 – 246
  12. Barreto, D.F., Takiya, C.M., Schatzmayr, G.H., Nogueira, R.M., Farias-Filho, J.C.,
  13. Barth OM. 2007. Histopathological and ultrastructural aspects of mice lungs experimentally infected with dengue virus serotype 2. Mem Inst Oswaldo Cruz, Rio de Janeiro, 102(2): 175-182
  14. Barth, O.M., Barreto, D.F, Paes, M.V., Takiya, C.M., Pinhao, A.T., Schatzmayr, G.H.2006. Morphological studies in a model for dengue-2 virus infection in mice. Mem Inst Oswaldo Cruz, Rio de Janeiro, 101(8): 905-915
  15. Kayesh MEH, Tsukiyama-Kohara K. Mammalian animal models for dengue virus infection: a recent overview. Archives of Virology (2022) 167:31–44
  16. Woonsung Na, Yeom M, Choi IK, Yook H, Song D. Animal models for dengie vaccines development and testing. Clin Exp Vaccine Res 2017;6:104-110
  17. Ruiz C.C, Barbosa H.G, Moreno S.M, Romero M.V, Chua J.V, Castellanos J.E, Zapata, J.C. Humanized Mice in Dengue Research: A Comparison with Other Mouse Model. Vaccines 2020, 8, 39
  18. Paes, M.V., Lenzi, H.L., Nogueira, A.C., Nuovo, G.J, Pinha, A.T., Mota, E.M., de- Oliveira, C.A., Schatzmayr, H., Barth, O.M., Alves, A.M. 2009. Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice. Laboratory Investigation, 89: 1140–1151
  19. Franca, R.F., Zucoloto, S., Fonseca, B.A. 2010. A BALB/c mouse model shows that liver involvement in dengue disease is immune-mediated. Experimental and Molecular Pathology, 89: 321–326
  20. da Costa Rasinhas, A.; Cunha Jácome, F.; Cardoso Caldas, G.; Teixeira de Almeida, A.L.; Nunes da Silva, M.A.; Dias Coutinho de Souza, D.; Carlos Paulino, A.; Mendes Bandeira, D.; Leonardo, R.; Conrado Guerra Nunes, P.; et al. Morphological Aspects and Viremia Analysis of BALB/c Murine Model Experimentally Infected with Dengue Virus Serotype 4. Viruses 2021, 13, 1954. v13101954
  21. Cardier, J.E., Marino, E., Romano, E., Taylor, P., Liprandi, F., Bosch, N., Rothman, A.L. 2005. Proinflammatory factors present in sera from patients with acute dengue infection induced activation and apoptosis of human microvascular endothelial cells: Possible role of TNFα in endothelial cell damage in dengue. Cytokine, 30: 359-365
  22. Conroy, A.L., Gelvez, M., Hawkes, M., Rajwan, M., Tran, V., Liles, W.C., Centeno, L.A., Kain, K.C. 2015. Host biomarkers are associated with progression to dengue haemorrhagic fever: a nested case-control study. International Journal of Infectious Disease, 40: 45-53
  23. Khongphatthanayothin A, Phumaphuti P, Thongchaiprasit K, Poovorawan Y. Serum Levels of sICAM-1 and sE-selectin in Patients with Dengue Virus Infections. Jpn.J.Infect.Dis, 59, 186-188, 2006
  24. Cardier, J.E., Rivas, B., Romano, E. 2006. Evidence of Vascular Damage in Dengue Disease: Demonstration of High Levels of Soluble Cell Adhesion Molecules and Circulating Endothelial Cells. Endothelium, 13: 335-340
  25. Yeh T-M, Liu S-H, Lin K-C, Kuo C, Kuo S-Y, et al. (2013) Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways. PLoS ONE 8(1): e55018. doi: 10.1371/journal.pone.0055018
  26. Malavige, G.N., Ogg, G.S. 2017. Pathogenesis of Vascular Leak in Dengue Virus Infection. John Wiley & Sons Ltd, Immunology, 151: 261–269

Last update:

No citation recorded.

Last update:

No citation recorded.