Showing papers by "Colin A. Russell published in 2018"
TL;DR: Recent advances in understanding the molecular determinants of influenza virus immune escape, sources of evolutionary selection pressure, population dynamics of influenza viruses and prospects for better influenza virus control are discussed.
Abstract: Despite decades of surveillance and pharmaceutical and non-pharmaceutical interventions, seasonal influenza viruses continue to cause epidemics around the world each year. The key process underlying these recurrent epidemics is the evolution of the viruses to escape the immunity that is induced by prior infection or vaccination. Although we are beginning to understand the processes that underlie the evolutionary dynamics of seasonal influenza viruses, the timing and nature of emergence of new virus strains remain mostly unpredictable. In this Review, we discuss recent advances in understanding the molecular determinants of influenza virus immune escape, sources of evolutionary selection pressure, population dynamics of influenza viruses and prospects for better influenza virus control.
446 citations
TL;DR: This corrects the article DOI: 10.1038/nrmicro2017.118 to indicate that the author of the paper is a PhD student at the University of Wisconsin-Madison, rather than a professor.
Abstract: Nature Reviews Microbiology http://dx.doi.org/10.1038/nrmicro.2017.118 (2017) In Figure 4 of the original online version of the article, the influenza virus epidemic activity by month was incorrectly labelled. This has now been corrected in the online and print versions. We apologize to the authors and to readers for any confusion caused.
60 citations
TL;DR: Phylogenetic analysis of regions spanning 80% of the genome showed that up to 13 viral clades have been circulating in the United Kingdom and that most of these are continuing to circulate, and bioinformatic analysis suggested that recombination has occurred between EHV‐1 clades, between E hv‐1 and equine herpesvirus 4, and between EhV‐ 1 and equinesvirus 8.
Abstract: Equine herpesvirus 1 (EHV-1) causes respiratory disease, abortion, neonatal death and neurological disease in equines and is endemic in most countries The viral factors that influence EHV-1 disease severity are poorly understood, and this has hampered vaccine development However, the N752D substitution in the viral DNA polymerase catalytic subunit has been shown statistically to be associated with neurological disease This has given rise to the term "neuropathic strain," even though strains lacking the polymorphism have been recovered from cases of neurological disease To broaden understanding of EHV-1 diversity in the field, 78 EHV-1 strains isolated over a period of 35 years were sequenced The great majority of isolates originated from the United Kingdom and included in the collection were low passage isolates from respiratory, abortigenic and neurological outbreaks Phylogenetic analysis of regions spanning 80% of the genome showed that up to 13 viral clades have been circulating in the United Kingdom and that most of these are continuing to circulate Abortion isolates grouped into nine clades, and neurological isolates grouped into five Most neurological isolates had the N752D substitution, whereas most abortion isolates did not, although three of the neurological isolates from linked outbreaks had a different polymorphism Finally, bioinformatic analysis suggested that recombination has occurred between EHV-1 clades, between EHV-1 and equine herpesvirus 4, and between EHV-1 and equine herpesvirus 8
32 citations
TL;DR: It is demonstrated that BCR diversity is affected by relationships between antibody variable and constant regions leading to isotype-specific signatures of variable gene usage, which provides powerful insights into the mechanisms underlying the evolution of the adaptive immune responses in health and their aberration during disease.
Abstract: A diverse B-cell receptor (BCR) repertoire is required to bind a wide range of antigens. BCRs are generated through genetic recombination and can be diversified through somatic hypermutation (SHM) or class-switch recombination (CSR). Patterns of repertoire diversity can vary substantially between different health conditions. We use isotype-resolved BCR sequencing to compare B-cell evolution and class-switch fate in healthy individuals and in patients with chronic lymphocytic leukemia (CLL). We show that the patterns of SHM and CSR in B-cells from healthy individuals are distinct from CLL. We identify distinct properties of clonal expansion that lead to the generation of antibodies of different classes in healthy, malignant, and non-malignant CLL BCR repertoires. We further demonstrate that BCR diversity is affected by relationships between antibody variable and constant regions leading to isotype-specific signatures of variable gene usage. This study provides powerful insights into the mechanisms underlying the evolution of the adaptive immune responses in health and their aberration during disease.
20 citations
TL;DR: PhyCLIP was developed to provide a statistically-principled phylogenetic clustering framework that negates the need for an arbitrarily-defined distance threshold and can be generalised to a wide variety of research questions concerning the identification of biologically informative clusters in pathogen phylogenies.
Abstract: Sub-species nomenclature systems of pathogens are increasingly based on sequence data. The use of phylogenetics to identify and differentiate between clusters of genetically similar pathogens is particularly prevalent in virology from the nomenclature of human papillomaviruses to highly pathogenic avian influenza (HPAI) H5Nx viruses. These nomenclature systems rely on absolute genetic distance thresholds to define the maximum genetic divergence tolerated between viruses designated as closely related. However, the phylogenetic clustering methods used in these nomenclature systems are limited by the arbitrariness of setting intra- and inter-cluster diversity thresholds. The lack of a consensus ground truth to define well-delineated, meaningful phylogenetic subpopulations amplifies the difficulties in identifying an informative distance threshold. Consequently, phylogenetic clustering often becomes an exploratory, ad-hoc exercise. Phylogenetic Clustering by Linear Integer Programming (PhyCLIP) was developed to provide a statistically-principled phylogenetic clustering framework that negates the need for an arbitrarily-defined distance threshold. Using the pairwise patristic distance distributions of an input phylogeny, PhyCLIP parameterises the intra- and inter-cluster divergence limits as statistical bounds in an integer linear programming model which is subsequently optimised to cluster as many sequences as possible. When applied to the hemagglutinin phylogeny of HPAI H5Nx viruses, PhyCLIP was not only able to recapitulate the current WHO/OIE/FAO H5 nomenclature system but also further delineated informative higher resolution clusters that capture geographically-distinct subpopulations of viruses. PhyCLIP is pathogen-agnostic and can be generalised to a wide variety of research questions concerning the identification of biologically informative clusters in pathogen phylogenies. PhyCLIP is freely available at http://github.com/alvinxhan/PhyCLIP.
17 citations
TL;DR: In simulated phylogenies, Phydelity achieves higher rates of correspondence to ground-truth clusters than current model-based methods, and comparable results to parametric methods without the need for parameter calibration.
Abstract: Current phylogenetic clustering approaches for identifying pathogen transmission clusters are limited by their dependency on arbitrarily-defined genetic distance thresholds for within-cluster divergence. Incomplete knowledge of a pathogen9s underlying dynamics often reduces the choice of distance threshold to an exploratory, ad-hoc exercise that is difficult to standardise across studies. Phydelity is a new tool for the identification of transmission clusters in pathogen phylogenies. It identifies groups of sequences that are more closely-related than the ensemble distribution of the phylogeny under a statistically-principled and phylogeny-informed framework, without the introduction of arbitrary distance thresholds. Relative to other distance threshold-based and model-based methods, Phydelity outputs clusters with higher purity and lower probability of misclassification in simulated phylogenies. Applying Phydelity to empirical datasets of hepatitis B and C virus infections showed that Phydelity identified clusters with better correspondence to individuals that are more likely to be linked by transmission events relative to other widely-used non-parametric phylogenetic clustering methods without the need for parameter calibration. Phydelity is generalisable to any pathogen and can be used to identify putative direct transmission events. Phydelity is freely available at https://github.com/alvinxhan/Phydelity.
15 citations
TL;DR: This work highlights priority areas where improved surveillance and outbreak mitigation could enhance pandemic preparedness strategies and identifies regions of Southeast Asia, Eastern Europe, Central America, and sub-Saharan Africa with high potential for influenza virus spillover.
Abstract: Background Avian and swine influenza viruses circulate worldwide and pose threats to both animal and human health. The design of global surveillance strategies is hindered by information gaps on the geospatial variation in virus emergence potential and existing surveillance efforts. Methods We developed a spatial framework to quantify the geographic variation in outbreak emergence potential based on indices of potential for animal-to-human and secondary human-to-human transmission. We then compared our resultant raster model of variation in emergence potential with the global distribution of recent surveillance efforts from 359105 reports of surveillance activities. Results Our framework identified regions of Southeast Asia, Eastern Europe, Central America, and sub-Saharan Africa with high potential for influenza virus spillover. In the last 15 years, however, we found that 78.43% and 49.01% of high-risk areas lacked evidence of influenza virus surveillance in swine and domestic poultry, respectively. Conclusions Our work highlights priority areas where improved surveillance and outbreak mitigation could enhance pandemic preparedness strategies.
2 citations