Infection of young adult mice with dengue virus type 2

Abstract

Young adult female mice, five to six weeks old, were injected intraperitoneally with 2.5 x 10(6.3) LD50 of dengue-2 virus, New Guinea C strain. The mice were killed on day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, and 35 respectively. By means of the immunofluorescent antibody technique, viral antigen appeared as irregular granules in the reticuloendothelial cells of liver, lymph nodes and spleen of infected mice on the first day after inoculation and then diminished. From the fifth to sixth day of infection dengue antigen appeared again as homogeneous staining in the cytoplasm of single or groups of mononuclear cells in the lymphatic sinuses only. Later, by the third week of infection, dengue antigen could be seen in the mononuclear cells located in the marginal zone of lymphoid follicle of the spleen, the pattern of staining changing to bright spherical granules. At the same time, the deposition of immune complexes (composed of dengue antigen, mouse gamma and beta 1C globulin) could be seen in the renal glomeruli of infected mice. Serum antibody to dengue virus was found at low levels, being maximal on the 14th day after infection. Dengue virus was not isolated from the sera or from the infected organs. Granulomatous inflammation developed in lymph nodes and liver of mice infected with dengue virus and in mice inoculated with normal mouse brain suspension. Proliferative glomerular lesion was observed on day 14 after inoculation without definite abnormal urine findings.

Morphological studies in a model for dengue-2 virus infection in mice

“…aiming to amplify the number of virus particles. Other studies using experimental mouse models (Bhamarapravati et al 1964, Boonpucknavig et al 1981, Nath et al 1983, Shresta et al 2004 were not able to caracterize the viremia, probably due to low levels of circulating DENV.…”

“…In studies with Swiss albino mice inoculated intraperitoneally with a neuroadapted virus, DENV antigen antibody complement complexes were located in the glomeruli, but without any significant effect on the glomerular function (Boonpucknavig et al 1981). Increase of mesangial cells was observed in DF human cases (Bhamarapravati 1997).…”

“…Studies on laboratory mice and non-human primates remain the most wellcharacterized models (Cole & Wisseman 1969, Marchette et al 1973, Boonpucknavig et al 1981, Hotta et al 1981a,b, Chaturvedi et al 1991, Wu et al 1995.…”

Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice

“…On the other hand, several mouse models have been described for dengue studies, although none of them were able to mimic the full spectrum of the disease. 4,10,14,[16][17][18][19][20][21][22][23][24][25] Difficulties are the result of many factors, including the inability of human clinical isolates to replicate well in mice, which frequently are overcome by the use of brain-mouse adapted viruses, non-physiological routes of infection and the use of immunodeficient and/or humanized animals. 4,16,17,24,25 Although these models are useful for many studies with DENV, they all have limitations, especially because of a loss of some human pathogenic properties that may not reflect natural events.…”

Pathobiology of the Flaviviruses

“…The only lower mammal that manifests a viscerotropic response to YF virus similar to monkeys and humans is the European hedgehog (Erinaceus europeaus) (Findlay and Clarke, 1934). Boonpucknavig et al (1981) studied the course of clinically inapparent dengue viral infection of adult outbred mice inoculated by the intraperitoneal route. Virus could not be isolated from tissues, but viral antigen was found by immunofluorescence in mononuclear leukocytes as late as 3 weeks after inoculation.…”