Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells

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Viral rewiring of cellular lipid metabolism to create membranous replication compartments

Positive-strand RNA (+RNA) viruses (e.g. poliovirus, hepatitis C virus, dengue virus, SARS-coronavirus) remodel cellular membranes to form so-called viral replication compartments (VRCs), which are the sites where viral RNA genome replication takes place. To induce VRC formation, these viruses extensively rewire lipid metabolism. Disparate viruses have many commonalities as well as disparities in their interactions with the host lipidome and accumulate specific sets of lipids (sterols, glycerophospholipids, sphingolipids) at their VRCs. Recent years have seen an upsurge in studies investigating the role of lipids in +RNA virus replication, in particular of sterols, and uncovered that membrane contact sites and lipid transfer proteins are hijacked by viruses and play pivotal roles in VRC formation

Viral rewiring of cellular lipid metabolism to create membranous replication compartments

Positive-strand RNA (+RNA) viruses (e.g. poliovirus, hepatitis C virus, dengue virus, SARS-coronavirus) remodel cellular membranes to form so-called viral replication compartments (VRCs), which are the sites where viral RNA genome replication takes place. To induce VRC formation, these viruses extensively rewire lipid metabolism. Disparate viruses have many commonalities as well as disparities in their interactions with the host lipidome and accumulate specific sets of lipids (sterols, glycerophospholipids, sphingolipids) at their VRCs. Recent years have seen an upsurge in studies investigating the role of lipids in +RNA virus replication, in particular of sterols, and uncovered that membrane contact sites and lipid transfer proteins are hijacked by viruses and play pivotal roles in VRC formation

The life cycle of non-polio enteroviruses and how to target it (vol 16, pg 368, 2018)

In the version of this Review originally published, co-author Hendrik Jan Thibaut's name was incorrectly indexed as "Jan Thibaut, H". It should have appeared as "Thibaut, HJ". This has now been corrected in all versions of the Review. The publisher apologizes to the authors and to readers for this error.status: publishe

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs

Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine.

A novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included-for the first time to our knowledge-the assessment of genetic heterogeneity using next-generation sequencing (NGS). NGS ensures that the genetically-modified regions of the vaccine virus genome remain as designed and that levels of polymorphisms which may impact safety or efficacy are controlled during routine production. The variants present in nOPV2 lots were first assessed for temperature sensitivity and neurovirulence using molecular clones to inform which polymorphisms warranted formal evaluation during lot release. The novel use of NGS as a lot release test required formal validation of the method. Analysis of an nOPV2 lot spiked with the parental Sabin-2 strain enabled performance characteristics of the method to be assessed simultaneously at over 40 positions in the genome. These characteristics included repeatability and intermediate precision of polymorphism measurement, linearity of both spike-induced and nOPV2 lot-specific polymorphisms, and the limit-of-detection of spike-induced polymorphisms. The performance characteristics of the method met pre-defined criteria for 34 spike-induced polymorphic sites and 8 polymorphisms associated with the nOPV2 preparation; these sites collectively spanned most of the viral genome. Finally, the co-location of variants of interest on genomes was evaluated, with implications for the interpretation of NGS discussed