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Rose, K.

Publications and source records attributed to Rose, K..

24 records · Page 2Linked to original sources

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission

The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, MVB biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101:VPS28:VPS37B:MVB12A was determined, revealing an ESCRT-I helical assembly with a 12 molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse grained simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding, and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor, but has an essential scaffolding and mechanical role in its own right.

biophysics↗

Metagenomic discovery and co-infection of diverse wobbly possum disease viruses and novel hepaciviruses in Australian brushtail possums

BackgroundAustralian brushtail possums (Trichosurus vulpecula) are an introduced pest species in New Zealand, but native to Australia where they are protected for biodiversity conservation. Wobbly possum disease (WPD) is a fatal neurological disease of Australian brushtail possums described in New Zealand populations that has been associated with infection by the arterivirus (Arteriviridae) wobbly possum disease virus (WPDV-NZ). Clinically, WPD-infected possums present with chronic meningoencephalitis, choroiditis and multifocal neurological symptoms including ataxia, incoordination, and abnormal gait. MethodsWe conducted a retrospective investigation to characterise WPD in native Australian brushtail possums, and used a bulk meta-transcriptomic approach (i.e. total RNA-sequencing) to investigate its potential viral aetiology. PCR assays were developed for case diagnosis and full genome recovery in the face of extensive genetic variation. ResultsWe identified a distinct lineage of arteriviruses from archival tissues of WPD-infected possums in Australia, termed wobbly possum disease virus AU1 and AU2. Phylogenetically, WPDV-AU1 and WPDV-AU2 shared only [~]70% nucleotide similarity to each other and the WPDV-NZ strain, suggestive of a relatively ancient divergence. Notably, we identified a novel and divergent hepacivirus (Flaviviridae) - the first in a marsupial - in both WPD-infected and uninfected possums, indicative of virus co-infection. ConclusionsWe have identified a distinctive marsupial-specific lineage of arteriviruses in mainland Australia that is genetically distinct from that in New Zealand, in some cases co-infecting animals with a novel hepacivirus. Our study provides new insight into the hidden genetic diversity of arteriviruses, the capacity for virus co-infection, and highlights the utility of meta-transcriptomics for disease investigation and surveillance in a One Health context.

pathology↗

Matryoshka RNA virus 1: a novel RNA virus associated with Plasmodium parasites in human malaria

Parasites of the genus Plasmodium cause human malaria. Yet nothing is known about the viruses that infect these divergent eukaryotes. We investigated the Plasmodium virome by performing a meta-transcriptomic analysis of blood samples from malaria patients infected with P. vivax, P. falciparum or P. knowlesi. This revealed a novel bi-segmented narna-like RNA virus restricted to P. vivax and named Matryoshka RNA virus 1 (MaRNAV-1) to reflect its \"Russian doll\" nature: a virus, infecting a parasite, infecting an animal. MaRNAV-1 was abundant in geographically diverse P. vivax from humans and mosquitoes. Notably, a related virus (MaRNAV-2) was identified in Australian birds infected with a Leucocytozoon - eukaryotic parasites that group with Plasmodium in the Apicomplexa subclass hematozoa. This is the first report of a Plasmodium virus. As well as broadening our understanding of the eukaryotic virosphere, the restriction to P. vivax may help understand P. vivax-specific biology in humans and mosquitoes.

evolutionary biology↗

Physical activity in children and adolescents with Charcot-Marie-Tooth disease: A cross-sectional case-controlled study

BackgroundDisability related to the progressive and degenerative neuropathies known as Charcot-Marie-Tooth disease (CMT) affects gait and function, increasing with age and influencing physical activity in adults with CMT. The relationship between disease, ambulatory function and physical activity in children and adolescents with CMT is unknown.\n\nMethodA cross-sectional case-controlled study of 50 children with CMT and age- and gender-matched typically developing (TD) controls [mean age 12.5 (SD 3.9) years]. A 7-day recall questionnaire assessed physical activity; disease severity and gait-related function were measured to explore factors associated with physical activity.\n\nResultsChildren with CMT were less active than TD controls (estimated weekly moderate to vigorous physical activity CMT 283.6 (SD 211.6) mins, TD 318.0 (SD 202.5) mins; p < 0.001). The children with CMT had moderate disability [CMT Pediatric Scale mean score 20 (SD 8) /44] and reduced ambulatory capacity in a six-minute walk test [CMT 485.1 (SD 160.9) metres, TD 639.8 (83.1) metres; p < 0.001]. Physical activity correlated with greater disease severity ({rho} = -0.52, p < 0.001) and six-minute walk distance ({rho} = 0.71, p < 0.001).\n\nConclusionsDisease-related disability affects physical activity and gait-related function in children and adolescents with CMT compared to TD peers. Reduced physical activity adversely affects function across the timespan of childhood and adolescence into adulthood.

neuroscience↗

Extensive Diversity of RNA Viruses in Australian Ticks

Understanding the microbiome of ticks in Australia is of considerable interest given the ongoing debate over whether Lyme disease, and its causative agent the bacterium Borrelia burgdorferi senso lato, are present in Australia. The diversity of bacteria infecting Australian ticks has been the subject of a number of studies using both culture and metagenomics based techniques. However, little is known about the virome of Australian ticks, including those that may have the potential to infect mammalian species. We used a meta-transcriptomics approach to reveal the viral diversity within Australian ticks collected from two locations on the central-east coast of Australia, including metropolitan Sydney. From this we identified 19 novel species of RNA virus belonging to 10 families, as well as one previously described RNA virus. The majority of these viruses clustered phylogenetically with arthropod-associated viruses suggesting that they do not utilize mammalian hosts. However, two novel viruses discovered in ticks feeding on bandicoot marsupials clustered closely within the mammalian associated Hepacivirus and Pestivirus genera (Flaviviridae). Notably, another bandicoot tick yielded a novel Coltivirus (Reoviridae) - a group of largely tick-associated viruses containing the known human pathogen Colorado tick fever virus and its relative Eyach virus. Importantly, our transcriptomic data provided no evidence for the presence of B. burgdorferi s.l.. in any tick sample, providing further evidence against the presence of Lyme Disease in Australia. In sum, this study reveals that Australian ticks harbor a diverse virome, including some viruses that merit additional screening in the context of emerging infectious disease.\n\nIMPORTANCEEach year a growing number of individuals along the east coast of Australia experience debilitating disease following tick bites. As there is no evidence for the presence of the causative agent of Lyme disease, Borrelia Burgdorferi seno lato, in Australian ticks, the etiological basis of this disease syndrome remains controversial. To characterize the viruses associated with Australian ticks, particularly those that might be associated with mammalian infection, we performed unbiased RNA sequencing on 146 ticks collected across two locations along the coast of New South Wales, Australia. This revealed 19 novel RNA viruses from a diverse set of families. Notably, three of these viruses were related to known mammalian viruses, including one that fell within the genus Coltivirus and related to the human pathogen, Colorado tick fever virus.

microbiology↗

Predicting E. coli concentrations using limited qPCR deployments at Chicago beaches

Culture-based methods to measure Escherichia coli (E. coli) are used by beach administrators to inform whether bacteria levels represent an elevated risk to swimmers. Since results take up to 12 hours, statistical models are used to forecast bacteria levels in lieu of test results; however they underestimate days with elevated fecal indicator bacteria levels. Quantitative polymerase chain reaction (qPCR) tests return results within 3 hours but are 2 to 5 times more expensive than culture-based methods. This paper presents a prediction model which uses limited deployments of qPCR tested sites with inter-beach correlation to predict when bacteria will exceed acceptable thresholds. The model can be used to inform management decisions on when to warn residents or close beaches due to exposure to the bacteria. Using data from Chicago collected between 2006 and 2016, the model proposed in this paper increased sensitivity from 3.4 percent to 11.2 percent-a 230 percent increase. We find that the correlation between beaches are substantial enough to provide higher levels of precision and sensitivity to predictive models. Thus, limited deployments of qPCR testing can be used to deliver better predictions for beach administrators at lower cost and less complexity.

bioinformatics↗