RACK1 associates with RNA-binding proteins Vigilin and SERBP1 to control dengue virus replication

Abstract

Dengue virus (DENV), a re-emerging virus transmitted by Aedes mosquitoes, causes severe pathogenesis in humans. No effective treatment is available against this virus. We recently identified the scaffold protein RACK1 as a component of the DENV replication complex, a macromolecular complex essential for viral genome amplification. Here, we show that RACK1 is important for DENV infection. RACK1 mediates DENV replication through binding to the 40S ribosomal subunit. Mass spectrometry analysis of RACK1 partners coupled to a loss-of-function screen identified the RNA binding proteins Vigilin and SERBP1 as DENV host dependency factors. Vigilin and SERBP1 interact with DENV viral RNA (vRNA), forming a ternary complex with RACK1 to mediate viral replication. Overall, our results indicate that RACK1 recruits Vigilin and SERBP1, linking the DENV vRNA to the translation machinery for optimal translation and replication.

Dehydration alters transcript levels in the mosquito midgut, likely facilitating rapid rehydration

“…This may offer additional insight into the reasons behind reduced egg production observed in dehydrated mosquitoes [7], or potentially into the veiled 20hydroxyecdysone (20E) signaling pathway. Another over-expressed gene of interest identified in our Y1_Y7 comparison, vigilin (AAEL001421-RA), has been implicated in the formation of RACK1, which is involved in viral RNA binding for DENV genome amplification [59]. Considering the abundance of RNA-involved processes in our Y7_N7 comparison, especially regarding our Y1_N1 comparison, possibilities exist for interactions between imbibed pathogens and the genes expressed within dehydrated mosquitoes.…”