Wild-Type Human Adenovirus (Serotype 31)

Here, researchers investigated the metabolic and molecular mechanisms of adipogenesis induced by human adenovirus type 31 (HAdV31). Using 3T3L1 cells (mouse embryonic fibroblasts, an adipogenic cell line) as a surrogate model, the increased proliferation, differentiation, and maturation of preadipocytes after infection with human adenoviruses were analyzed. The expression of E4orf1, C/EBP-β, PPAR-γ, GAPDH, aP2, LEP, and fatty acid synthase genes, intracellular lipid accumulation, and cytokine release from adipocytes were evaluated. The data showed that HAdV31 increased the expression of C/EBP-β and PPAR-γ genes, thereby promoting the differentiation of preadipocytes into adipocytes. In addition, the overexpression of GAPDH and fatty acid synthase and the reduction of leptin expression led to increased intracellular lipid accumulation. TNF-α and IL-6 secretion was significantly reduced after HAdV31 infection of cells, resulting in unlimited viral replication. These findings demonstrate that HAdV31 is a subsequent human adenovirus that is able to affect the differentiation and lipid accumulation of 3T3L1 cells.

After replication of the HAdV31 virus, the expression of C/EBP-b and PPAR-g increased on days 5 and 10 after inoculation (Figure 1a, b). The synergistic action of these genes activated the transcription of genes involved in adipocyte phenotype determination, differentiation, intracellular binding of fatty acids, and fatty acid absorption and storage. HAdV31 infection also led to a significant increase in GAPDH expression in 3T3L1 cells compared with the negative control and uninfected controls (Figure 1c). Unfortunately, the expression of aP2 (indicating its ability to accumulate intracellular lipids) in cells infected with HAdV31 was not higher than that in cells infected with HAdV5 or uninfected controls (Figure 1d). This observation was similar to that in the positive control, so the virus-infected adipocytes may require longer culture to achieve the desired effect, but this remains to be verified. The researchers analyzed the expression of FAS to confirm that the replication of HAdV31 was able to induce faster and more significant differentiation of adipocytes. The expression of fatty acid synthase in 3T3L1 cells infected with HAdV31 was significantly higher than that in negative and uninfected controls (Figure 1e). Furthermore, preadipocytes infected with HAdV31 had decreased transcription of leptin, similar to AdV36 (Figure 1f).

Figure 1. Gene expression of 3T3L1 cells inoculated with adenoviruses. (Bil‐Lula I, et al., 2016)