..4. Discussion Symptoms and selleck chem Imatinib signs of dengue fever include sudden onset of high fever, retroorbital headache, rash, joint and muscle pain, some degree of hemorrhage, low platelet counts and liver damage. Several immunodeficient animal models have been described to study different aspects of the disease [7, 9, 10, 14]. Several animal models have been used to study the disease, including immunocompetent [6, 8] immunocompromised [7, 9] and humanized mice [15]. However, it is well known that the immune system combats an invading pathogen by a very complex interplay between the many different components of this system; thus, important interplay between those components can be masked by the immunodeficiency induced in those animals, leading, in some cases, to misleading conclusions.

In this study, we have established an experimental model of DENV infection using immunocompetent C57BL/6 mice, which showed some signs of DF similar to those observed in human. Moreover, the animals became viremic and the virus spread to several organs.Approximately, one-third of DF patients may have mild hemorrhage manifestations, which may be related to the low platelet count [5]. Then, platelet count is a useful marker to be evaluated in an animal model during DENV infection. In that sense, our C57BL/6 mice model showed a significant thrombocytopenia between seven and ten days after DENV-1 infection. In other studies, H. C. Chen, (2007), and Y. T. Yen, (2008), have also shown that C57BL/6 mice infected with DENV-2 showed a significant thrombocytopenia and severe systemic hemorrhage when a very high viral dose (2 �� 109PFU) was used for the infection, but no hemorrhage was observed at lower viral dose (4 �� 107PFU).

In our study, we did not analyze in more details the presence of hemorrhage, but macroscopic hemorrhage was observed in the spleen of the infected animals.After the mosquito biting, human skin dendritic cells (Langerhans cells) are one of the first targets for DENV infection [15�C18]. Then, the virus spread systemically infecting several organs. In that sense, DENV has been found in different Anacetrapib organs such as skin [19], liver [20�C22], spleen [21�C23], lymph nodes [21, 22], kidney [22, 24], bone marrow [22, 24], lung [22, 24], thymus [25], and brain [26]. The animal model analyzed in our study showed the presence of viral genome in kidney, liver, spleen and brain after infection. Although liver is not a major target organ, several studies have demonstrated elevated liver enzyme levels in human serum indicating the damage of this organ after DENV infection [27�C30]. Hepatitis associated with dengue fever is also characterized by moderate hepatocytes necrosis, microvesicular steatosis and cellular infiltration [31�C33].