Wild-Type Human Adenovirus (Serotype 14)

Human adenovirus (HAdV) can cause severe respiratory symptoms in immunocompromised people, and there is currently no targeted treatment for adenovirus infection. Selenium (Se) plays an important role in antioxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of selenium is mainly achieved through conversion to selenocystine (SeC). Selenium participates in the active sites of various selenoproteins in the form of SeC. In recent years, SeC has attracted much attention due to its unique antioxidant activity. The antiviral ability of SeC was determined by detecting the infection rate of the virus in cells. Here, researchers designed SeC to resist A549 cell infection caused by human adenovirus type 14 (HAdV-14). SeC can prevent DNA damage-related cell apoptosis caused by HAdV-14. SeC significantly inhibited the generation of ROS and protected cells from ROS-induced oxidative damage of HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway and repaired DNA damage by inhibiting the ATR, p53, and PARP signaling pathways. Therefore, SeC may provide an effective selenium species with antiviral properties for the therapies against HAdV-14.

The apoptosis rates of the control group and the SeC-treated group were 2.7% and 5.0%, and the necrosis rates were 1.3% and 2.7%, respectively, while the apoptosis and necrosis rates of the virus group were 12.6% and 24.2%, respectively. After SeC treatment, the apoptosis and necrosis rates of A549 cells infected with HAdV-14 were significantly reduced, similar to those of the control group (Figure 1A). The changes in intracellular fluorescence were observed by fluorescence microscopy, which was consistent with the results of flow cytometry (Figure 1B). These results indicate that HAdV-14 infection causes the normal cell cycle of A549 cells to be disrupted, thereby mediating the cells to enter the apoptosis and necrosis stages. SeC can effectively alleviate the apoptosis and necrosis caused by HAdV-14 infection. A549 cells infected with HAdV-14 showed obvious nuclear deformation and DNA fragmentation, and DNA fragmentation mainly occurred in the nucleus. After SeC treatment, DNA fragmentation in the nucleus of A549 cells infected with HAdV-14 was significantly reduced (Figure 1C). In addition, compared with the control group, the TUNEL fluorescence intensity of the virus group increased significantly to 289.3%, while the fluorescence intensity of the Virus+SeC group decreased significantly to 137.1% (Figure 1D). These results indicate that SeC can prevent genomic DNA damage caused by HAdV-14.

Figure 1. Inhibitory effect of SeC on apoptosis and DNA fragmentation induced by HAdV-14 infection. (Zheng R, et al., 2023)