Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice.
One difficulty in studying dengue virus (DENV) is the lack of an experimental model that reproduces the human disease. In a previous work, we have shown that BALB/c mice intraperitoneally inoculated with a DENV-2 isolate presented viremia and mild focal areas of liver injuries. In this study, mice were inoculated by the intravenous route and presented extensive damage areas in the liver tissue, which were evaluated by histopathological and ultrastructural analysis. Hepatic injury was noted mainly around the central vein and portal tracts. Damages consist of hepatocyte injury, including steatosis, swelling and necrosis. Further, erythrophagocytosis, intercellular edema and vascular damages were evident, including hemorrhage, which is characteristic of the dengue-induced hepatitis in human liver. Hepatic lesions were already noted 2 days post infection (p.i.), although effects were more extensive after the seventh day p.i. An increase in alanine aminotransferase and aspartate aminotransferase serum levels was detected 7 and 14 days p.i., respectively, and had correlation to hepatic lesions. Alterations caused by the DENV infection were self-limiting, with a remarkable reduction of all liver damages 49 days p.i. Virus antigens were detected in hepatocytes, Kupffer cells and vascular endothelium, suggesting virus replication in these cells. In situ hybridization, using a probe that anneals in the virus negative RNA strand, showed positive reaction in hepatocytes and vascular endothelium cells of infected mice, thus confirming virus replication in such cells. In general, results revealed that this mouse model reproduces some histopathological effects observed in humans and supports previous findings indicating virus replication in the hepatic tissue.
Paes
Marciano Viana
MV
Laboratório de Biotecnologia e Fisiologia de Infecções Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Lenzi
Henrique Leonel
HL
Nogueira
Ana Cristina Martins
AC
Nuovo
Gerard James
GJ
Pinhão
Angela Teixeira
AT
Mota
Ester Maria
EM
Basílio-de-Oliveira
Carlos Alberto
CA
Schatzmayr
Hermann
H
Barth
Ortrud Monika
OM
Alves
Ada Maria de Barcelos
AM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000097:blood; D003715:Dengue / Q000097:blood / Q000473:pathology* / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000032:analysis*; D014779:Virus Replication
D000956:Antigens, Viral; D012367:RNA, Viral; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase