Maintenance of a host-specific minority mutation in the West Nile virus NS3.

West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes.

The Role of the Flavivirus Replicase in Viral Diversity and Adaptation.

Flaviviruses include several emerging and re-emerging arboviruses which cause millions of infections each year. Although relatively well-studied, much remains unknown regarding the mechanisms and means by which these viruses readily alternate and adapt to different hosts and environments. Here, we review a subset of the different aspects of flaviviral biology which impact host switching and viral fitness.

Streamlined Whole-Genome Sequencing of Mumps Virus for High-Resolution Outbreak Analysis.

Since 2015, the United States has experienced a resurgence in the number of mumps cases and outbreaks in fully vaccinated populations. These outbreaks have occurred predominantly in close-quarter settings, such as camps, colleges, and detention centers. Phylogenetic analysis of 758 mumps-positive samples from outbreaks across the United States identified 743 (98%) as genotype G based on sequence analysis of the mumps small hydrophobic (SH) gene.

A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide.

The naturally occurring nucleotide 3'-deoxy-3',4'-didehydro-cytidine-5'-triphosphate () was recently found to exert potent and broad-spectrum antiviral activity. However, nucleoside 5'-triphosphates in general are not cell-permeable, which precludes the direct use of as a therapeutic. To harness the therapeutic potential of this endogenous antiviral nucleotide, we synthesized phosphoramidate prodrug HLB-0532247 () and found it to result in dramatically elevated levels of in cells.

Divergent Mutational Landscapes of Consensus and Minority Genotypes of West Nile Virus Demonstrate Host and Gene-Specific Evolutionary Pressures.

Our current understanding of the natural evolution of RNA viruses comes largely from consensus level genetic analyses which ignore the diverse mutant swarms that comprise within-host viral populations. The breadth and composition of viral mutant swarms impact viral fitness and adaptation, and the capacity for swarm plasticity is likely to be particularly important for arthropod-borne viruses (arboviruses) that cycle between taxonomically divergent hosts. Despite this, characterization of the relationship between the selective pressures and genetic signatures of the mutant swarm and consensus sequences is lacking.

West Nile Virus fidelity modulates the capacity for host cycling and adaptation.

The fidelity of flaviviruses is thought to be tightly regulated for optimal fitness within and between hosts. West Nile virus (WNV) high-fidelity (HiFi) mutations V793I and G806R within the RNA-dependent RNA polymerase, and low-fidelity (LoFi) mutation T248I within the methyltransferase, were previously shown to attenuate infectivity and replicative fitness in mosquitoes and (CXT) cells but not in mammalian cells. We hypothesized that fidelity alterations would modify adaptation and maintenance in a host-specific manner.

Different cognitive profiles for single compared with recurrent fallers without dementia.

Relationships between self-reported retrospective falls and cognitive measures (executive function, reaction time [RT], processing speed, working memory, visual attention) were examined in a population based sample of older adults (n = 658). Two of the choice RT tests involved inhibiting responses to either targets of a specific color or location with hand and foot responses. Potentially confounding demographic variables, medical conditions, and postural sway were controlled for in logistic regression models, excluding participants with possible cognitive impairment.

Comparison of self-reported crashes, state crash records and an on-road driving assessment in a population-based sample of drivers aged 69-95 years.

Objective: The study evaluated associations between outcome measures used in driving research including self-reported crashes, state crash records, and an on-road driving test (ORT).

Method: A total of 750 community dwelling participants aged 69 to 95 were recruited via the electoral roll into a study on injury prevention. Of these, 509 were drivers, and data on self-reported crashes, and either state crash records, or an on-road assessment were available for 488.