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PNAS Studies Examine Influenza B Evolution, Endogenous Retroviruses, More

Researchers in Singapore, India, Australia, and the US describe distinct evolutionary routes for co-circulating influenza B viruses from the "Victoria" and "Yamagata" lineages. The team focused on more than 12,000 available influenza B genomes — along with 158 newly sequenced flu viruses from clinical isolates from hospitals in Singapore — to retrace the evolutionary history of hemagglutinin, neuraminidase, and other genes in flu viruses from the lineages, which emerged in the 1970s, but become more common flu epidemic contributors more recently. "We show that following prolonged diversification, both lineages underwent selective sweeps across the genome and have subsequently taken alternate evolutionary trajectories to exhibit epidemic dominance," the authors report, "with no reassortment between lineages."

APOBEC3 genes coding for antiviral components may have been amplified in mammalian genomes in response to endogenous retroviruses (ERVs), according to a team from Japan and the UK. By analyzing more than 1,400 APOBEC-related genes found in 160 mammalian genomes, the researchers saw increasing APOBEC3 gene amplification and expansion as ERV representation rose. Moreover, the authors note that characteristic mutations introduced by APOBEC3 appear particularly common in the ERV sequences found in mammals carrying such expansions "We demonstrate that ancient, fossilized retrovirus sequences in mammalian genomes contain clear signatures of A3-mediated mutation," they write, "and provide several additional lines of evidence that A3 evolution has been driven by long-running conflicts with ancient retroviruses."

Researchers at Harvard, the Broad Institute, and elsewhere take a look at the transcriptional, cell state, and subtype changes that accompany treatment response in pancreatic ductal adenocarcinoma (PDAC). Using RNA sequencing, RNA in situ hybridization, and other approaches, the team assessed PDAC tumors or cell lines exposed to different treatments. While FOLFIRINOX combination treatment appeared to prompt a recurrent shift toward cell states that are increasingly similar to the quasi-mesenchymal PDAC subtype, for example, the authors saw PDAC subtype-specific responses to another drug. "Understanding and monitoring the fluidity of PDAC [epithelial] and [quasi-mesenchymal subtype] states are critical to the development of improved clinical trial design to target these different subpopulations," the authors note.