Infection with dengue virus presents a broad clinical spectrum, which can range from asymptomatic cases to severe cases that are characterised by haemorrhagic syndrome and/or shock. The reason for such variability remains unknown. This work evaluated the in vitro permissiveness of mouse, rat, hamster and guinea pig macrophages to infection by dengue virus 2 (DENV2). The results established that macrophages derived from the BALB/c mouse strain showed higher permissiveness to DENV2 infection than macrophages from other rodent species, although all rodent species studied had the C820T mutation in the oligoadenylate synthetase 1b gene, indicating no relationship to the different in vitro susceptibilities of mouse cells at this locus. Other molecular mechanisms related to flavivirus susceptibility remain to be explored. 1. Introduction Infection with dengue virus (DENV) causes dengue and severe dengue (formerly dengue fever and dengue haemorrhagic fever). DENV belongs to the Flaviviridae family, flavivirus genus. DENV is an enveloped virus, and its genome consists of a positive polarity, single-stranded RNA of around 11？kb that encodes ten proteins. DENV can replicate in several types of cells, including dendritic cells, B and T lymphocytes, endothelial cells, hepatocytes, and neuronal cells. However, monocytes/macrophages are the primary target during in vivo infection [1]. Viral entry into these cells enables the virus to spread to different tissues and induces the presentation HLA molecule-associated viral antigens. The presentation of viral antigens by macrophages to memory T cells induces T cell activation and, consequently, the proliferation and production of cytokines such as TNF-α, IFN, and IL-2. This set of cytokines and chemokines induces endothelial dysfunction and plasma leakage, both of which are characteristic of more severe manifestations of the disease [2]. Several studies have addressed the relationship between human genes and the susceptibility to dengue virus infection. For example, the HLA-A*0203 allele correlated with dengue fever (DF) in Thai children, while HLA-A*0207 correlated with dengue haemorrhagic fever (DHF). Moreover, the alleles HLA-B44, B62, B76, and B77 confer protection against DHF in secondary infections [3]. Other polymorphisms associated with DHF have been found in the genes for DC-SIGN1, TNF-α, Fc-γ receptors, vitamin D receptors, and mannose binding lectin [4, 5]. In addition to these host factors, there is evidence that DENV serotypes 2 and 3 cause DHF more frequently [6], supporting the belief that both host and
References
[1]
K. Clyde, J. L. Kyle, and E. Harris, “Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis,” Journal of Virology, vol. 80, no. 23, pp. 11418–11431, 2006.
[2]
Y. C. Chen and S. Y. Wang, “Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide,” Journal of Virology, vol. 76, no. 19, pp. 9877–9887, 2002.
[3]
H. A. F. Stephens, R. Klaythong, M. Sirikong et al., “HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais,” Tissue Antigens, vol. 60, no. 4, pp. 309–318, 2002.
[4]
M. T. Fernández-Mestre, K. Gendzekhadze, P. Rivas-Vetencourt, and Z. Layrisse, “TNF-α-308A allele, a possible severity risk factor of hemorrhagic manifestation in dengue fever patients,” Tissue Antigens, vol. 64, no. 4, pp. 469–472, 2004.
[5]
H. Loke, D. Bethell, C. X. T. Phuong et al., “Susceptibility to dengue hemorrhagic fever in Vietnam: evidence of an association with variation in the vitamin D receptor and FCγ receptor IIA genes,” The American Journal of Tropical Medicine and Hygiene, vol. 67, no. 1, pp. 102–106, 2002.
[6]
A. Balmaseda, S. N. Hammond, L. Pérez et al., “Serotype-specific differences in clinical manifestations of dengue,” The American Journal of Tropical Medicine and Hygiene, vol. 74, no. 3, pp. 449–456, 2006.
[7]
T. Mashimo, M. Lucas, D. Simon-Chazottes et al., “A nonsense mutation in the gene encoding 2′-5′-oligoadenylate synthetase/L1 isoform is associated with West Nile virus susceptibility in laboratory mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 17, pp. 11311–11316, 2002.
[8]
A. A. Perelygin, S. V. Scherbik, I. B. Zhulin, B. M. Stockman, Y. Li, and M. A. Brinton, “Positional cloning of the murine flavivirus resistance gene,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 14, pp. 9322–9327, 2002.
[9]
S. V. Scherbik, K. Kluetzman, A. A. Perelygin, and M. A. Brinton, “Knock-in of the Oas1br allele into a flavivirus-induced disease susceptible mouse generates the resistant phenotype,” Virology, vol. 368, no. 2, pp. 232–237, 2007.
[10]
M. Lucas, T. Mashimo, M. P. Frenkiel et al., “Infection of mouse neurones by West Nile virus is modulated by the interferon-inducible 2′-5′ oligoadenylate synthetase 1b protein,” Immunology and Cell Biology, vol. 81, no. 3, pp. 230–236, 2003.
[11]
C. Lynch and T. Hughes, “The inheritance of susceptibility to Yellow Fever encephalitis in mice,” Genetics, vol. 21, pp. 104–112, 1937.
[12]
L. Pantelic, H. Sivakumaran, and N. Urosevic, “Differential induction of antiviral effects against west nile virus in primary mouse macrophages derived from flavivirus-susceptible and congenic resistant mice by alpha/beta interferon and poly(I-C),” Journal of Virology, vol. 79, no. 3, pp. 1753–1764, 2005.
[13]
J. Prada-Arismendy and J. E. Castellanos, “Real time PCR. Application in dengue studies,” Colombia Médica, vol. 42, pp. 243–258, 2011.
[14]
S. N. Peirson, J. N. Butler, and R. G. Foster, “Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis,” Nucleic Acids Research, vol. 31, no. 14, article e73, 2003.
[15]
J. A. Mosquera, J. P. Hernandez, N. Valero, L. M. Espina, and G. J. A？ez, “Ultrastructural studies on dengue virus type 2 infection of cultured human monocytes,” Virology Journal, vol. 2, article 26, 2005.
[16]
J. Prada-Arismendy and J. E. Castellanos, “Susceptibility/Resistance genes to Flavivirus, implications on disease severity,” Acta Biológica Colombiana, vol. 11, pp. 21–30, 2006.
[17]
A. Sabin, “Nature of inherited resistance to viruses affecting the nervous system,” Proceedings of the National Academy of Sciences, vol. 38, pp. 540–546, 1952.
[18]
N. Urosevic, M. Van Maanen, J. P. Mansfield, J. S. Mackenzie, and G. R. Shellam, “Molecular characterization of virus-specific RNA produced in the brains of flavivirus-susceptible and -resistant mice after challenge with Murray Valley encephalitis virus,” Journal of General Virology, vol. 78, no. 1, pp. 23–29, 1997.
[19]
M. A. Brinton, “Analysis of extracellular West Nile virus particles produced by cell cultures from genetically resistant and susceptible mice indicates enhanced amplification of defective interfering particles by resistant cultures,” Journal of Virology, vol. 46, no. 3, pp. 860–870, 1983.
[20]
L. M. Espina, N. J. Valero, J. M. Hernández, and J. A. Mosquera, “Increased apoptosis and expression of tumor necrosis factor-α caused by infection of cultured human monocytes with dengue virus,” The American Journal of Tropical Medicine and Hygiene, vol. 68, no. 1, pp. 48–53, 2003.
[21]
J. T. Jan, B. H. Chen, S. H. Ma et al., “Potential dengue virus-triggered apoptotic pathway in human neuroblastoma cells: arachidonic acid, superoxide anion, and NF-κB are sequentially involved,” Journal of Virology, vol. 74, no. 18, pp. 8680–8691, 2000.
[22]
T. Matsuda, A. Almasan, M. Tomita et al., “Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand,” Journal of General Virology, vol. 86, no. 4, pp. 1055–1065, 2005.
[23]
W. H. Kwan, E. Navarro-Sanchez, H. Dumortier et al., “Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth,” PLoS Neglected Tropical Diseases, vol. 2, no. 10, Article ID e311, 2008.
