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PLOS Papers Describe Host Factors Needed for Coronavirus Replication, Pathways Influencing RSV Severity, More

Researchers from Switzerland and Germany have used two CRISPR knock-out screens to uncover host factors that are necessary for coronavirus replication. In a new paper in PLOS Biology, they report on their genome-wide CRISPR/Cas-9 knockout screens of HCoV-229E — which causes mild disease — and MERS-CoV — which is highly pathogenic — within human cell lines to identify host dependency factors. Many of the top genes they identified are involved in autophagy, and existing drugs that inhibit the autophagy-linked immunophilin proteins could also inhibit coronavirus replication in cell culture, they found. "Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs," the researchers write.

In a multi-omic analysis, researchers from the University of Rochester Medical Center homed in on a link between respiratory syncytial virus severity and certain immune signaling pathways. They collected peripheral blood and nasal samples from 139 infants with RT-PCR-confirmed RSV disease for additional transcriptome and microbiome analyses. As they report in PLOS Computational Biology, the researchers combined this data with nine measures of clinical severity to calculate a Global Respiratory Severity Score. Through this, they further found a link between disease severity and pathways controlling Th17 activation and the inhibition of B cell receptor signaling. "These novel data can guide future efforts to identify sensitive and specific biomarkers for identifying or predicting outcome following infant RSV infection," the Rochester team writes.

Lastly, an Institut Pasteur-led team has uncovered a high level of genetic diversity among Leptospira species in Laos. About 1 million people a year develop leptospirosis, of whom about 60,000 die. By sequencing 75 different Leptospira strains isolated from patients, the team uncovered 11 different serogroups and 43 core genome multi-locus sequence typing-defined clonal groups, as they report in PLOS Neglected Tropical Diseases. The most common of those clonal groups was CG272, which the researchers note was found among a large outbreak in nearby Thailand. "Concerted control efforts targeting CG272/ST34 isolates specifically could reduce epidemic and endemic risks of leptospirosis in Southeast Asia," the researchers add.