Identification of Differentially Expressed Genes in BALB/c Mouse Liver upon Primary Infection with DENV1 and Sequential Heterologous Infection with DENV2

Abstract

Dengue virus (DENV) results in 100 million cases of infections and 22,000 deaths per year. Liver involvement, thrombocytopenia, haemorrhage and plasma leakage are characteristic manifestations of severe forms of DENV infection. However, the molecular pathways of DENV infection have not been comprehensively studied compared to the host immunological responses. We performed an in vivo study using the BALB/c mouse model with a modified mRNA differential display methodology (GeneFishingTM) using the annealing control primer (ACP) system to capture differentially expressed genes (DEGs) in mice liver upon primary infection with DENV1 and sequential heterologous infection with DENV2. Secondary heterologous infection with DENV2 was carried out at Immunoglobulin IgM and IgG peaks following the primary DENV1 infection with the hope of determining any potential effect antibodies IgM and IgG may have on sequential heterologous infection. 30 DEGs were identified and sequenced across all three treatment groups and they belong to a variety of important pathways such as apoptosis, innate immune response, inflammatory response, metabolic processes and oxidative stress. Analysis of differentially expressed genes in response to viral infection offers valuable knowledge about the dynamic and complex association between host cell and the virus. Furthermore, some DEGs identified support DENV induced liver damage.

MicroRNA profiling of mouse liver in response to DENV-1 infection by deep sequencing

“…(2005), hepatic injury in DENV-2 infected BALB/c mice was observed as early as 2 d.p.i, and at the 3 d.p.i, hepatocytes showed diffused steatosis in midzonal areas, while at 7 d.p.i, necrosis and a strong flux of edema was observed. The DENV-1 used in this study was able to evoke inflammatory immune responses as evidenced by the enlargement of spleen and liver (data not shown) and most importantly by the rise of DENV-1 specific IgM and IgG (Wickremsinghe et al, 2018). Here, we also demonstrated that there were differential expressions in the regulating miRNAs during DENV-1 infection.…”

“…Evidence that DENV-1 infection was established in the mice was based on the development of IgM and IgG antibodies at various days post infection to determine the peak levels of IgM and IgG (Wickremsinghe et al, 2018). Three six-week old male BALB/c mice were infected with DENV-1.…”