Putative prefoldin complex subunit 5 of Plasmodium berghei is crucial for microtubule formation and parasite development in the mosquito.

Plasmodium sporozoite development in and egress from oocysts in the Anopheles mosquito remains largely enigmatic. In a previously performed high-throughput knockout screen, the putative subunit 5 of the prefoldin complex (PbPCS5, PBANKA_0920100) was identified as essential for parasite development during mosquito and liver stage development. Here we generated and analyzed a PbPCS5 knockout parasite line during its development in the mosquito. Interestingly, PbPCS5 deletion does not significantly affect oocyst formation but leads to a growth defect resulting in aberrantly shaped sporozoites. Sporozoites produced in the absence of PbPCS5 were thinner, markedly elongated, and did, in most cases, not contain a nucleus. Sporozoites contained fewer subpellicular microtubules, which reached deep into the sporoblast during sporogony where they contacted and indented nuclei. These aberrantly shaped sporozoites did not reach the salivary glands, and we, therefore, conclude that PbPCS5 is essential for sporogony and the life cycle progression of the parasite during its mosquito stage.

Manipulation of Type I Interferon Signaling by HIV and AIDS-Associated Viruses.

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.

Cadmium potentiates toxicity of cypermethrin in zebrafish.

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.