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Cell Papers on Tumor Cell States, Rift Valley Fever Virus Host Factors, Recombinant SARS-CoV-2

Stanford University researchers present tumor cell and corresponding ecosystem profiles produced using a machine learning tool called EcoTyper, designed for characterizing cell states based on gene expression data. When the team applied EcoTyper to expression data for 16 human carcinoma types, for example, it detected 69 cell states spanning a dozen cell lineages as well as 10 related multicellular ecosystems of co-occurring cell states that provided additional clinical clues. "Most [cell] states were specific to neoplastic tissue, ubiquitous across tumor types, and significantly prognostic," the authors report, adding that they saw "unexpectedly strong conservation" within the 10 ecosystem communities, "including three with myeloid and stromal elements linked to adverse survival, one enriched in normal tissue, and two associated with early cancer development."

A Washington University- and University of Pittsburgh-led team reports on host factors that appear to help the Rift Valley fever virus (RVFV) make its way into mouse cells. The researchers narrowed in on the receptor-associated protein (RAP), a heat shock protein called Grp94, and the low-density lipoprotein receptor-related protein 1 (Lrp1) as RVFV infection contributors in a genome-wide CRISPR screen in mice. In their follow-up experiments, they explored RVFV interactions with Lrp1 in particular, demonstrating that RVFV infections can be dampened down in mice and other potential RVFV hosts by introducing soluble viral glycoproteins, antibodies, or other ligands that can bind to Lrp1. "Together," the authors write, "these data support Lrp1 as a host entry factor for RVFV infection and define a new target to limit RVFV infections."

Finally, investigators in the UK and the US consider SARS-CoV-2 recombination patterns in samples of the coronavirus collected in the UK, focusing on isolates initially classified in the B.1.1.7 lineage. Based on some 279,000 SARS-CoV-2 sequences, the team tracked down 16 recombinant genomes containing both B.1.1.7 and non-B.1.1.7 sequences, which appeared to stem from eight recombination events. "In four instances, there was evidence of onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of [two] months," they write. "The inferred genomic locations of recombination breakpoints suggest that ever community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations."