Co-occurrence of pesticides such as synthetic pyrethroids and metals in aquatic ecosystems raises concerns over their combined ecological effects. Cypermethrin, 1 of the top 5 synthetic pyrethroids in use, has been extensively detected in surface water. Cadmium (Cd) has been recognized as 1 of the most toxic metals and is a common contaminant in the aquatic system. However, little information is available regarding their joint toxicity. In the present study, combined toxicity of cypermethrin and Cd and the underlying mechanisms were investigated. Zebrafish embryos and adults were exposed to the individual contaminant or binary mixtures. Co-exposure to cypermethrin and Cd produced synergistic effects on the occurrence of crooked body, pericardial edema, and noninflation of swim bladder. The addition of Cd significantly potentiated cypermethrin-induced spasms and caused more oxidative stress in zebrafish larvae. Cypermethrin-mediated induction of transcription levels and catalytic activities of cytochrome P450 (CYP) enzyme were significantly down-regulated by Cd in both zebrafish larvae and adults. Chemical analytical data showed that in vitro elimination of cypermethrin by CYP1A1 was inhibited by Cd. The addition of Cd caused an elevation of in vivo cypermethrin residue levels in the mixture-exposed adult zebrafish. These results suggest that the enhanced toxicity of cypermethrin in the presence of Cd results from the inhibitory effects of Cd on CYP-mediated biotransformation of this pesticide. The authors' findings provide a deeper understanding of the mechanistic basis accounting for the joint toxicity of cypermethrin and Cd.
Type I Interferons were first described for their profound antiviral abilities in cell culture and animal models, and later, they were translated into potent antiviral therapeutics. However, as additional studies into the function of Type I Interferons progressed, it was also seen that pathogenic viruses have coevolved to encode potent mechanisms allowing them to evade or suppress the impact of Type I Interferons on their replication. For chronic viral infections, such as HIV and many of the AIDS-associated viruses, including HTLV, HCV, KSHV, and EBV, the clinical efficacy of Type I Interferons is limited by these mechanisms. Here, we review some of the ways that HIV and AIDS-associated viruses thrive in Type I Interferon-rich environments via mechanisms that block the function of this important antiviral cytokine. Overall, a better understanding of these mechanisms creates avenues to better understand the innate immune response to these viruses as well as plan the development of antivirals that would allow the natural antiviral effect of Type I Interferons to manifest during these infections.
Kaposi’s Sarcoma (KS) is an angioproliferative disease with symptoms including skin lesions that appear at different sites of the body caused by Kaposi’s Sarcoma Associated Herpesvirus (KSHV). The KSHV genome encodes genes pirated from the human genome that are homologous to cellular proteins that disrupt innate immune pathways. We have found a novel ORF in the KSHV genome that is homologous to the human IPS-1 protein. This viral IPS-1 proteins (vIPS-1) contains the PRO domain of IPS-1 but lacks the CARD and TM domains. We hypothesize that vIPS-1 is able to interact with the cellular TRAF3 protein. Western blot data shows that co-expression of vIPS-1 does not affect RIG-I, decreases the stability of human IPS-1 and TRIF, and increases the stability of TRAF3. Also, vIPS-1 interacts with TRAF3 via coimmunoprecipitation, and by co-expressing vIPS-1 with different TRAF3 mutants we found that vIPS-1 interacts with TRAF3 through the TRAF domain which is specifically required for TRAF3-mediated type I IFN production. Furthermore, our data shows that while expression of IPS-1 is able to inhibit VSV-GFP replication, expression of vIPS-1 significantly enhances the VSV-GFP replication, consistent with our hypothesis that vIPS-1 blocks the cellular immune responses. In conclusion, the KSHV vIPS-1 protein blocks antiviral immunity by interacting with TRAF3 leading to a decrease in antiviral activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.