Infection of five human liver cell lines by dengue-2 virus

Abstract

Elevated serum transaminase levels of dengue patients indicate the possible impact of dengue virus infection on liver function. To elucidate the action of dengue virus infection in liver cells, an in vitro cell line system was established that mimicked the liver status of diverse clinical patients. Briefly, four hepatoma cell lines (HA22T, Huh7, Hep3B, and PLC) and one nonmalignant hepatocyte cell line (Chang liver) were included, representing various levels of tumorigenicity and differentiation. Our data showed that in these five cell lines, dengue-2 virus attached to each cell type equally well; however, this virus had higher replication rates and levels of virion production in differentiated Huh7, PLC, Hep3B, and Chang liver cells. Likewise, a lower replication rate was observed in the de-differentiated HA22T cells. Differentiation-related factors seem to play an important role in dengue virus replication. Further study showed that sodium butyrate (NaB, a differentiation inducer) treatment enhanced dengue virus replication in HA22T cells. Moreover, we found that the severity of morphologic aberration and the increase in aspartate aminotransferase (AST) levels correlated with the virus replication rate in the four infected hepatoma cells. In conclusion, we showed that dengue virus can infect diverse liver cells with differing replication efficiency, which causes cytopathic effects (CPEs) of diverse severity. Among the CPEs, the increased AST levels correlated with the clinical results from 24 dengue fever patients, who showed increased AST levels at the onset of fever. In summary, we find that dengue-2 virus replicates actively and causes severe CPEs in differentiated hepatoma cells. Factors related to differentiation as well as tumorigenicity seem to play critical roles, though the mechanisms of action remain unclear.

Liver injury caused by antibodies against dengue virus nonstructural protein 1 in a murine model

“…DV can infect liver cells and cause damage. [30][31][32][33] Liver histopathology in fatal cases of DHF indicated that hepatocytes and Kupffer cells may be the target cells for viral replication and that an apoptotic mechanism was involved. 50 The autoantibodies present in dengue patient sera, 37 however, showed no crossreactivity with liver cell lines tested, including Chang liver, HA22T, and Huh7 cells.…”

“…Elevated serum levels of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are signs of liver dysfunction in DHF patients. 14,15,[27][28][29] A previous study 30 indicated that the severity of cytopathic effects and the increase in AST levels correlated with the virus replication rate in DV-infected liver cell lines. Further studies [31][32][33] showed cell activation and apoptosis in DV-infected liver cell lines.…”

Overexpressed in anaplastic thyroid carcinoma‐1 (OEATC‐1) as a novel gene responsible for anaplastic thyroid carcinoma

“…Judging from the results, OEATC-1 seems to be responsible for various types of disease progression, but its contribution may differ according to carcinoma type. In particular, ACLs were undifferentiated and had aggressive phenotypes compared with the differentiated cell line Huh7, 14 suggesting that the expression OEATC-1 is dependant on the grade of biologic or histologic differentiation.…”

Dengue Virus Infection Induced NF-κB-dependent Macrophage Migration Inhibitory Factor Production

“…However, in cells from the human hepatoma HepG2 cell line, which is also permissive to DV2 infection [17] , DV2 infection did not induce the release of MIF. Therefore, not all cells permissive to DV2 infection will release MIF after DV2 infection.…”