Cleavage of the syncytial protein of J paramyxovirus is required for its ability to promote cell-cell fusion.

Cell-cell fusion mediated by most paramyxovirus requires fusion protein (F) and attachment protein (H, HN, or G). The F protein is proteolytic cleaved to be fusogenically active. J paramyxovirus (JPV) has a unique feature in the family Paramyxoviridae: It encodes an integral membrane protein, syncytial protein (SP, formerly known as transmembrane protein, TM), which is essential in JPV-promoted cell-cell fusion (i.e., syncytial). In this study, we report that cleavage of SP is essential for its syncytial-promoting activity. We have identified the cleavage site of SP at amino acid residues 172 to 175, LKTG, and deletion of the "LKTG" residues abolished SP protein cleavage and its ability to promote cell-cell fusion. Replacing the cleavage site LKTG with a factor Xa protease cleavage site allows cleavage of the SP with factor Xa protease and restores its ability to promote cell-cell fusion. Furthermore, results from a hemifusion assay indicate that cleavage of SP plays an important role in the progression from the intermediate hemifusion state to a complete fusion. This work indicates that SP has many characteristics of a fusion protein. We propose that SP is likely a cell-cell fusion-promoting protein.

Enteric Populations of Escherichia coli are Likely to be Resistant to Phages Due to O Antigen Production.

Bioinformatic and experimental data show that bacteriophages are ubiquitous in human enteric microbiomes. However, there are gaps in understanding the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how these phages are maintained over time. To address these questions, we adapted and analyzed the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage and performed experiments with Escherichia coli and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota. Our models predict and experiments confirm that due to production of the O antigen, E. coli in the enteric microbiome are likely to be resistant to infection with co-occurring phages. However, phages can be maintained in these populations in high densities due to high rates of transition between resistant and sensitive states, which we call leaky resistance. Based on these models and observations, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of E. coli in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in enteric microbiota is not yet clear, although O antigen production is broadly conserved across many taxa.