A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R0 from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R0. \ud \ud Data and Methods. On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions. \ud \ud Findings. We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R0 of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R0 in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population. \ud \ud Interpretation: Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed

Armadillo 1.1: An Original Workflow Platform for Designing and Conducting Phylogenetic Analysis and Simulations

In this paper we introduce Armadillo v1.1, a novel workflow platform dedicated to designing and conducting phylogenetic studies, including comprehensive simulations. A number of important phylogenetic and general bioinformatics tools have been included in the first software release. As Armadillo is an open-source project, it allows scientists to develop their own modules as well as to integrate existing computer applications. Using our workflow platform, different complex phylogenetic tasks can be modeled and presented in a single workflow without any prior knowledge of programming techniques. The first version of Armadillo was successfully used by professors of bioinformatics at Université du Quebec à Montreal during graduate computational biology courses taught in 2010–11. The program and its source code are freely available at: <http://www.bioinfo.uqam.ca/armadillo>

SHIV-162P3 Infection of Rhesus Macaques Given Maraviroc Gel Vaginally Does Not Involve Resistant Viruses

Maraviroc (MVC) gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0) but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294±0.027%; limited entropy changes were noted across the envelope (gp160). No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14–21, the time of first detectable viremia, nor selected at later time points, days 42–70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC50] 1.87 nM) and virus isolated from the three MVC-treated macaques (MVC IC50 1.18 nM, 1.69 nM, and 1.53 nM, respectively). Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants

Assessing the Value of DNA Barcodes for Molecular Phylogenetics: Effect of Increased Taxon Sampling in Lepidoptera

BACKGROUND: A common perception is that DNA barcode datamatrices have limited phylogenetic signal due to the small number of characters available per taxon. However, another school of thought suggests that the massively increased taxon sampling afforded through the use of DNA barcodes may considerably increase the phylogenetic signal present in a datamatrix. Here I test this hypothesis using a large dataset of macrolepidopteran DNA barcodes. METHODOLOGY/PRINCIPAL FINDINGS: Taxon sampling was systematically increased in datamatrices containing macrolepidopteran DNA barcodes. Sixteen family groups were designated as concordance groups and two quantitative measures; the taxon consistency index and the taxon retention index, were used to assess any changes in phylogenetic signal as a result of the increase in taxon sampling. DNA barcodes alone, even with maximal taxon sampling (500 species per family), were not sufficient to reconstruct monophyly of families and increased taxon sampling generally increased the number of clades formed per family. However, the scores indicated a similar level of taxon retention (species from a family clustering together) in the cladograms as the number of species included in the datamatrix was increased, suggesting substantial phylogenetic signal below the 'family' branch. CONCLUSIONS/SIGNIFICANCE: The development of supermatrix, supertree or constrained tree approaches could enable the exploitation of the massive taxon sampling afforded through DNA barcodes for phylogenetics, connecting the twigs resolved by barcodes to the deep branches resolved through phylogenomics

Complete Genome Sequence of Crohn's Disease-Associated Adherent-Invasive E. coli Strain LF82

International audienceBACKGROUND: Ileal lesions of Crohn's disease (CD) patients are abnormally colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells and macrophages. PRINCIPAL FINDINGS: We report here the complete genome sequence of E. coli LF82, the reference strain of adherent-invasive E. coli associated with ileal Crohn's disease. The LF82 genome of 4,881,487 bp total size contains a circular chromosome with a size of 4,773,108 bp and a plasmid of 108,379 bp. The analysis of predicted coding sequences (CDSs) within the LF82 flexible genome indicated that this genome is close to the avian pathogenic strain APEC_01, meningitis-associated strain S88 and urinary-isolated strain UTI89 with regards to flexible genome and single nucleotide polymorphisms in various virulence factors. Interestingly, we observed that strains LF82 and UTI89 adhered at a similar level to Intestine-407 cells and that like LF82, APEC_01 and UTI89 were highly invasive. However, A1EC strain LF82 had an intermediate killer phenotype compared to APEC-01 and UTI89 and the LF82 genome does not harbour most of specific virulence genes from ExPEC. LF82 genome has evolved from those of ExPEC B2 strains by the acquisition of Salmonella and Yersinia isolated or clustered genes or CDSs located on pLF82 plasmid and at various loci on the chromosome. CONCLUSION: LF82 genome analysis indicated that a number of genes, gene clusters and pathoadaptative mutations which have been acquired may play a role in virulence of AIEC strain LF82

Rapid identification of bovine MHCI haplotypes in genetically divergent cattle populations Using Next-Generation Sequencing

The major histocompatibility complex (MHC) region contains many genes that are key regulators of both innate and adaptive immunity including the polymorphic MHCI and MHCII genes. Consequently, the characterisation of the repertoire of MHC genes is critical to understanding the variation that determines the nature of immune responses. Our current knowledge of the bovine MHCI repertoire is limited with only the Holstein-Friesian breed having been studied in any depth. Traditional methods of MHCI genotyping are of low resolution and laborious and this has been a major impediment to a more comprehensive analysis of the MHCI repertoire of other cattle breeds. Next-generation sequencing (NGS) technologies have been used to enable high throughput and much higher resolution MHCI typing in a number of species. In this study we have developed a MiSeq platform approach and requisite bioinformatics pipeline to facilitate typing of bovine MHCI repertoires. The method was validated initially on a cohort of Holstein-Friesian animals and then demonstrated to enable characterisation of MHCI repertoires in African cattle breeds, for which there was limited or no available data. During the course of these studies we identified >140 novel classical MHCI genes and defined 62 novel MHCI haplotypes, dramatically expanding the known bovine MHCI repertoire