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This Week in Cell: Nov 16, 2016

The Ebola virus adapted to become more adept at infecting humans during the recent outbreak in West Africa, according to a pair of Cell studies by independent teams. For the first of these, researchers in France, the UK, and elsewhere used information from more than 1,600 Ebola virus genomes sequenced from Guinea, Sierra Leone, Liberia, and Mali between 2013 and 2016 to develop synthetic glycoproteins from early stages of the outbreak, systematically adding amino acid substitutions corresponding to lineages subsequently described in West Africa. With pseudoviruses containing the synthetic glycoproteins, the team demonstrated that such substitutions seemed to spur tropism for human cells.

For their part, investigators from the US and UK centered their analyses on a form of mutant Ebola glycoprotein known as A82V, which is believed to have become far more common over the course of the outbreak. That team's results suggest that glycoprotein A82V was better adapted to human dendritic cells and other primate cells than versions of the virus containing glycoprotein sequences found previously due to enhanced interactions with a viral receptor called NPC1. "The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the [Ebola virus] interface," the authors note, "suggesting that this mutation was indeed an adaptation to the human host."

An international team takes a look at the human immune consequences of ancient mixing between humans and Neanderthals. In a search for immune regulatory features related to Neanderthal admixture, the researchers pinged African and European primary monocyte immune cells with bacterial stimuli or viral stimuli and then tracked responses with RNA sequencing. From there, they compared the two, since mixing with Neanderthals primarily appears to have occurred in non-African populations, and mapped expression quantitative trait loci related to Toll-like receptor pathway and other immune responses. From these and other experiments, the study's authors saw that "immune-responsive regulatory variants are enriched in population-specific signals of natural selection," while "admixture with Neanderthals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges."