Global progress in clinical research on human respiratory syncytial virus vaccines.

Human respiratory syncytial virus (hRSV) not only affects newborns but also older adults, contributing to a substantial worldwide burden of disease. However, only three approved hRSV vaccines remain commercially available to date. The development of a safe, practical and broad-spectrum vaccine suitable for all age groups remains extremely challenging. Using five different approaches-live-attenuated, recombinant-vector, subunit, particle-based, and mRNA-nearly 30 hRSV vaccine candidates are currently conducting clinical trials worldwide; moreover, > 30 vaccines are under preclinical evaluation. This review presents a comprehensive overview of these hRSV vaccines along with prospects for the development of infectious disease vaccines in the post-COVID-19 pandemic era.

Transfer RNA-Derived Small RNAs in the Pathogenesis of Parasitic Protozoa.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are newly identified non-coding small RNAs that have recently attracted attention due to their functional significance in both prokaryotes and eukaryotes. tsRNAs originated from the cleavage of precursor or mature tRNAs by specific nucleases. According to the start and end sites, tsRNAs can be broadly divided into tRNA halves (31-40 nucleotides) and tRNA-derived fragments (tRFs, 14-30 nucleotides). tsRNAs have been reported in multiple organisms to be involved in gene expression regulation, protein synthesis, and signal transduction. As a novel regulator, tsRNAs have also been identified in various protozoan parasites. The conserved biogenesis of tsRNAs in early-branching eukaryotes strongly suggests the universality of this machinery, which requires future research on their shared and potentially disparate biological functions. Here, we reviewed the recent studies of tsRNAs in several representative protozoan parasites including their biogenesis and the roles in parasite biology and intercellular communication. Furthermore, we discussed the remaining questions and potential future works for tsRNAs in this group of organisms.

Identification and Functional Characterization of Divergent 3'-Phosphate tRNA Ligase From Entamoeba histolytica.

HSPC117/RtcB, 3'-phosphate tRNA ligase, is a critical enzyme involved in tRNA splicing and maturation. HSPC117/RtcB is also involved in mRNA splicing of some protein-coding genes including XBP-1. Entamoeba histolytica, a protozoan parasite responsible for human amebiasis, possesses two RtcB proteins (EhRtcB1 and 2), but their biological functions remain unknown. Both RtcBs show kinship with mammalian/archaeal type, and all amino acid residues present in the active sites are highly conserved, as suggested by protein alignment and phylogenetic analyses. EhRtcB1 was demonstrated to be localized to the nucleus, while EhRtcB2 was in the cytosol. EhRtcB1, but not EhRtcB2, was required for optimal growth of E. histolytica trophozoites. Both EhRtcB1 (in cooperation with EhArchease) and EhRtcB2 showed RNA ligation activity in vitro. The predominant role of EhRtcB1 in tRNAIle(UAU) processing in vivo was demonstrated in EhRtcB1- and 2-gene silenced strains. Taken together, we have demonstrated the conservation of tRNA splicing and functional diversification of RtcBs in this amoebozoan lineage.