Resveratrol, a natural polyterpenoid, can scavenge reactive oxygen species in vivo to carry out the functions of antioxidation and antiaging. Resveratrol’s anti-cancer capability has attracted widespread attention, but its molecular mechanism has not been systematically explained. In this study, by comparing the activity of normal cell lines and cancer cell lines after treating with resveratrol, it was found that resveratrol has more significant cytotoxicity in cancer cell lines. Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. A total of 330 significantly differential genes were identified through large-scale transcriptome sequencing, among which 103 genes were upregulated and 227 genes were downregulated. Transcriptome and qRT-PCR data proved that a large number of genes related to cell cycle were differentially expressed after the treatment of resveratrol. The changes of cell cycle phases at different time points after treating with resveratrol were further detected, and it was found that the cells were arrested in the S phase because of the percentage of cells in S phase increased and cells in G1/G0 phase decreased. In conclusion, resveratrol can inhibit the proliferation of 4T1 cancer cells by inhibiting cell cycle and inducing apoptosis.

Solar ultraviolet radiation (UV) may cause DNA damage. We first report in this study that the large subunit ribosome protein RPL12, from Bomby mori (BmRPL12), participated in UV-induced DNA damage repair. BmRPL12 enhanced the resistance of Escherichia coli (E. coli) to UV radiation and facilitated faster repair of UV-induced DNA damage in silkworm cells. BmRPL12 mainly existed in the cytoplasm in the dimer forms, and the N-terminal nuclear export signal was crucial for the localization of BmRPL12. After UV radiation, BmRPL12 was unable to localize at the UV-induced DNA damage sites to participate in damage repair directly and might indirectly regulate UV-induced DNA damage repair. Our previous research found that BmNPV Bm65 was an important UV damage-induced endonuclease. Here, it was further found that in BmNPV-infected silkworm cells, BmRPL12 in monomeric forms interacted with the virus Bm65 protein only after UV radiation, and BmRPL12 specifically localized at the UV-induced DNA damage sites only in the presence of Bm65. We speculate that after viral infection in cells subjected to UV-induced DNA damage, viral protein Bm65 interacts with BmRPL12 and localizes BmRPL12 to sites of UV-damaged DNA.

Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, remain unknown. This protein is hypothesized to play a role in viral replication and pathogenesis. To investigate its structure and function, we employed phylogenetic analysis, subcellular localization, mutational analysis, and a dual-luciferase reporter system to characterize the nuclear localization signal (NLS) within NS2 and its effect on viral promoter activity. Additionally, co-immunoprecipitation and mass spectrometry were utilized to identify host proteins interacting with NS2. We identified a functional bipartite NLS in NS2, validated the combination pattern of key amino acids, and demonstrated its role in regulating viral promoter activity. Furthermore, we identified potential NLSs in NS2 homologs in other invertebrate ssDNA viruses based on sequence analysis. We also revealed interactions between NS2 and host nuclear transport proteins, suggesting that it plays a role in nuclear transport and viral replication. This research underscores the importance of NS2’s NLS in BmBDV’s life cycle and its potential conservation across invertebrate ssDNA viruses, providing insights into virus–host interactions and avenues for antiviral strategy development.

Snakehead vesiculovirus (SHVV), a strain of negative-stranded RNA viruses extracted from sick snakehead fish (Ophicephalus striatus), may pose a threat to the health of snakehead fish. Previous research has proved that the replication of SHVV can be significantly inhibited by glutamine starvation. To study how glutamine starvation inhibits SHVV replication, channel catfish ovary (CCO) cells with SHVV cultivated in the glutamine-free medium or the complete medium were used to investigate the differentially expressed proteins (DEPs). The results showed that 124 up-regulated and 246 down-regulated proteins were involved in many viral replication physiological processes, such as autophagy, post-translational modifications machinery, and functional pathways, including the PI3K-Akt signaling pathway and mTOR signaling pathway. Furthermore, a few proteins, such as Akt and Hsp90, which have been confirmed to be involved in the replication of RNA viruses, were also significantly differentially expressed. Taken together, our study demonstrated that glutamine starvation affects various functional pathways and the expression of some key proteins related to RNA viral replication, which will benefit future studies on the replication mechanisms of SHVV and the prevention of SHVV infection.

Bombyx mori bidensovirus (BmBDV) is a bipartite single-stranded DNA virus that causes severe losses in sericulture, yet its transcriptional complexity and possible self-regulatory viral small RNAs remain unexplored. Here, transcriptome and small RNA sequencing of BmBDV-infected midguts was performed to identify novel viral transcripts and functional virus-derived small RNAs (vsRNAs). A previously unrecognized transcript (transcript IV, nt 290–2929) was discovered on the VD1 segment, sharing its 5′ promoter region with NS2 and its 3′ polyadenylation signal with VP. Notably, the most abundant viral small RNA, a 20-nt vsRNA designated vsRNA-18895 (TPM up to 11,750), mapped to the promoter-overlap region shared by NS1, NS2 and transcript IV (VD1 nt 596–615). In vivo agomir/antagomir experiments showed that injection of a double-stranded RNA corresponding to vsRNA-18895 (an agomir) significantly upregulated NS1, NS2 and transcript IV (up to 103.52-, 102.47- and 101.87-fold, respectively) and enhanced VD1 replication (103.26-fold), whereas injection of a single-strand RNA complementary to vsRNA-18895 (an antagomir) suppressed them; VD2 and other viral genes (VP, PolB, NS3 and P133) were unaffected. Because the abundance of vsRNA-18895 itself was not directly measured following antagomir injection, this treatment may either reduce, or merely interfere with, the activity of the small RNA. These findings are consistent with a positive feedback loop in which a virus-encoded small RNA embedded in the promoter region of a novel transcript facilitates BmBDV replication, providing functional evidence of a self-regulatory vsRNA in an invertebrate single-stranded DNA virus. Because a complementary antisense small RNA produced from the same locus was of comparable abundance, a possible contribution of that strand to the observed effects cannot be excluded.