Virulence difference between red sea bream iridovirus mixed subtype I/II and subtype II and the expression of viral and apoptosis-related genes in infected rock bream (Oplegnathus fasciatus).

In this study, the virulence of the red sea bream iridovirus (RSIV) subtype II (17RbGs isolate) and a novel RSIV mixed subtype I/II (17SbTy isolate), which was genetically characterized in a previous study, were compared. The infectivity to rock bream (Oplegnathus fasciatus) determined by infectious dose (ID50) revealed that 17RbGs isolate was significantly more infective than 17SbTy isolate using both intraperitoneal injection and bath immersion. In a cohabitation challenge test that mimicked natural conditions, the cumulative mortality of the donor (RSIV-injected rock bream) and the recipient (cohabited naïve rock bream) was significantly higher in the 17RbGs group than in the 17SbTy group, regardless of RSIV injected doses, supporting the correlation between genetic mutation and pathogenicity. In addition, the maximum viral shedding ratio identified from RSIV-infected rock bream suggested that viral transmission through infection with the 17SbTy isolate could have a lower relative risk than that of infection with the 17RbGs isolate. In particular, the odds ratio based on the spleen index after 17RbGs infection was 55.00, which was inconsistent with that of 17SbTy infection (19.38), hence supporting the virulence difference between RSIVs. Furthermore, the expression of viral genes, including DNA membrane and myristoylated protein genes with insertion and deletion mutations, and that of caspase-8, which is related to caspase-dependent apoptosis induced by RSIV infection, were significantly upregulated at 11 days post 17RbGs-infection compared to that following 17SbTy infection. Notably, although viral genes were highly expressed in the early infection stage and caspase-8 was upregulated, the low caspase-3 expression may have inhibited apoptosis, reflecting the difference in virulence between different RSIV isolates. Several virulence factors, including pathogenicity, viral shedding ratio, odds ratio, and gene expression, support that RSIV mixed subtype I/II may be a less pathogenic RSIV isolate compared with general RSIV subtype II in a natural environment.

Jaceosidin, a pharmacologically active flavone derived from Artemisia argyi, inhibits phorbol-ester-induced upregulation of COX-2 and MMP-9 by blocking phosphorylation of ERK-1 and -2 in cultured human mammary epithelial cells.

Elevated levels of cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) are frequently found in various types of cancerous and transformed cells, with recent studies implicating the upregulation of COX-2 and MMPs in the development of breast cancer. This article investigated the effects of jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone) isolated from Artemisia argyi on the upregulation of COX-2 and MMP-9 induced by the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in MCF10A human breast epithelial cells (MCF10A cells). Treatment of MCF10A cells with TPA induced the upregulation of COX-2 and MMP-9, and this was attenuated by jaceosidin treatment. Jaceosidin also inhibited the invasive and migrative phenotypes of MCF10A cells induced by TPA. Furthermore, jaceosidin blocked the TPA-induced phosphorylation of extracellular signal-regulated protein kinase-1 and -2 (ERK-1 and -2), which is one of the signaling molecules regulating COX-2 and MMP. These results suggest that jaceosidin inhibits the TPA-induced upregulation of COX-2 and MMP-9 by blocking ERK-1 and -2 phosphorylation in human breast epithelial cells, which may be indicative of its chemopreventive potential.