Alvira : comparative genomics of viral strains

The Alvira tool is a general purpose multiple sequence alignment viewer with a special emphasis on the comparative analysis of viral genomes. This new tool has been devised specifically to address the problem of the simultaneous analysis of a large number of viral strains. The multiple alignment is embedded in a graph that can be explored at different levels of resolution

Aménagements hydro-agricoles et santé (vallée du fleuve Sénégal)

La ville de Richard-Toll offre sept types de points d'eau à sa population, allant du site ouvert non aménagé (fleuve) aux bornes offrant de l'eau canalisée. Les usagers y gèrent eux-mêmes leur réserve d'eau quotidienne. Pour évaluer l'effet du site d'approvisionnement et du comportement de l'usager sur la qualité de l'eau consommée, l'eau de 14 sites, représentant les sept types de points d'eau présents dans la ville, a été échantillonnée. De plus, quatre usagers ont été associés à chaque point d'eau, et leur eau a été analysée à domicile à trois reprises, soit après entreposage de moins d'une heure, de 8 heures et de 24 heures. Les analyses ont permis de déterminer la qualité bactériologique de l'eau (coliformes fécaux), qui s'est avérée être excellente (0-10 UCG par 100 ml) à 4 des 14 points d'eau, et mauvaise (101-500 UGC par 100 ml) ou très mauvaise (> 500 UGC par 100 ml) dans les autres cas. Après entreposage de moins d'une heure, l'eau à l'origine excellente a vu sa qualité se dégrader chez la moitié (8 des 16) des usagers, alors que l'eau de mauvaise et de très mauvaise qualité s'est améliorée chez 19 des 39 usagers. Durant l'entreposage quotidien normal de 24 heures, l'eau à l'origine d'excellente qualité s'est dégradée dans 14 des 16 cas, alors que l'eau à l'origine mauvaise ou très mauvaise, s'est améliorée de façon permanente dans 14 des 35 cas. La chloration de l'eau à domicile explique certaines améliorations (5 des 14 cas). Ces résultats démontrent que si la qualité dépend au départ du site d'approvisionnement, l'usager est en mesure de l'affecter de façon positive ou négative, et ce indépendamment de la situation de départ. (Résumé d'auteur

The human mycobiome in health and disease

The mycobiome, referring primarily to the fungal biota in an environment, is an important component of the human microbiome. Despite its importance, it has remained understudied. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal importance. An integrative analysis of current studies shows that different body sites harbor specific fungal populations, and that diverse mycobiome patterns are associated with various diseases. By interfacing with other biomes, as well as with the host, the mycobiome probably contributes to the progression of fungus-associated diseases and plays an important role in health and disease. © 2013 BioMed Central Ltd

Potential involvement of Brugia malayi cysteine proteases in the maintenance of the endosymbiotic relationship with Wolbachia

Brugia malayi, a parasitic nematode that causes lymphatic filariasis, harbors endosymbiotic intracellular bacteria, Wolbachia, that are required for the development and reproduction of the worm. The essential nature of this endosymbiosis led to the development of anti- Wolbachia chemotherapeutic approaches for the treatment of human filarial infections. Our study is aimed at identifying specific proteins that play a critical role in this endosymbiotic relationship leading to the identification of potential targets in the adult worms. Filarial cysteine proteases are known to be involved in molting and embryogenesis, processes shown to also be Wolbachia dependent. Based on the observation that cysteine protease transcripts are differentially regulated in response to tetracycline treatment, we focused on defining their role in symbiosis. We observe a bimodal regulation pattern of transcripts encoding cysteine proteases when in vitro tetracycline treated worms were examined. Using tetracycline-treated infertile female worms and purified embryos we established that the first peak of the bimodal pattern corresponds to embryonic transcripts while the second takes place within the hypodermis of the adult worms. Localization studies of the native proteins corresponding to Bm-cpl-3 and Bm-cpl-6 indicate that they are present in the area surrounding Wolbachia, and, in some cases, the proteins appear localized within the bacteria. Both proteins were also found in the inner bodies of microfilariae. The possible role of these cysteine proteases during development and endosymbiosis was further characterized using RNAi. Reduction in Bm-cpl-3 and Bm-cpl-6 transcript levels was accompanied by hindered microfilarial development and release, and reduced Wolbachia DNA levels, making these enzymes strong drug target candidates

A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene

BACKGROUND: Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes [1]. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates. METHODS: In the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major. RESULTS: A unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages. CONCLUSION: The present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates, the CL A2 gene is unique, lacking most of the nucleotide repeats that constitute the variable region at the 5'end of the VL A2 sequences. As the variable region of the VL A2 gene has been shown to correspond to a portion of the protein which is highly immunogenic, the present results support the hypothesis of a possible role of the A2 gene in the differential tropism of CL and VL leishmania parasites

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

A Genomic-Based Approach Combining In Vivo Selection in Mice to Identify a Novel Virulence Gene in Leishmania

Parasites of the genus Leishmania cause a variety of human diseases that range from destructive skin lesions caused by L. major to visceral infections of the liver and spleen caused by L. donovani that result in death. The Leishmania genes responsible for these different pathologies are not known. In the present study, we used a comparative genome-based approach to introduce and over-express L. donovani genes in L. major to determine whether this results in increased virulence of L. major in visceral organs of infected mice. Through this approach, a novel gene termed Li1040 was identified that is potentially involved in protein transport and was shown to increase pathogenesis in the visceral organs in mice. The Li1040 gene may therefore represent a Leishmania virulence gene that has the potential to regulate the pathology of infection in the mammalian host. These observations help to define how Leishmania causes fatal infections in humans and therefore provide a parasite-specific target for therapy

Intraseasonal Dynamics and Dominant Sequences in H3N2 Influenza

Long-term influenza evolution has been well studied, but the patterns of sequence diversity within seasons are less clear. H3N2 influenza genomes sampled from New York State over ten years indicated intraseasonal changes in evolutionary dynamics. Using the mean Hamming distance of a set of amino acid or nucleotide sequences as an indicator of its diversity, we found that influenza sequence diversity was significantly higher during the early epidemic period than later in the influenza season. Diversity was lowest during the peak of the epidemic, most likely due to the high prevalence of a single dominant amino acid sequence or very few dominant sequences during the peak epidemic period, corresponding with rapid expansion of the viral population. The frequency and duration of dominant sequences varied by influenza protein, but all proteins had an abundance of one distinct sequence during the peak epidemic period. In New York State from 1995 to 2005, high sequence diversity during the early epidemic suggested that seasonal antigenic drift could have occurred primarily in this period, followed by a clonal expansion of typically one clade during the peak of the epidemic, possibly indicating a shift to neutral drift or purifying selection