42 research outputs found

    IMG/VR: a database of cultured and uncultured DNA Viruses and retroviruses.

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    Viruses represent the most abundant life forms on the planet. Recent experimental and computational improvements have led to a dramatic increase in the number of viral genome sequences identified primarily from metagenomic samples. As a result of the expanding catalog of metagenomic viral sequences, there exists a need for a comprehensive computational platform integrating all these sequences with associated metadata and analytical tools. Here we present IMG/VR (https://img.jgi.doe.gov/vr/), the largest publicly available database of 3908 isolate reference DNA viruses with 264 413 computationally identified viral contigs from >6000 ecologically diverse metagenomic samples. Approximately half of the viral contigs are grouped into genetically distinct quasi-species clusters. Microbial hosts are predicted for 20 000 viral sequences, revealing nine microbial phyla previously unreported to be infected by viruses. Viral sequences can be queried using a variety of associated metadata, including habitat type and geographic location of the samples, or taxonomic classification according to hallmark viral genes. IMG/VR has a user-friendly interface that allows users to interrogate all integrated data and interact by comparing with external sequences, thus serving as an essential resource in the viral genomics community

    Cryoelectron Tomography of HIV-1 Envelope Spikes: Further Evidence for Tripod-Like Legs

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    A detailed understanding of the morphology of the HIV-1 envelope (Env) spike is key to understanding viral pathogenesis and for informed vaccine design. We have previously presented a cryoelectron microscopic tomogram (cryoET) of the Env spikes on SIV virions. Several structural features were noted in the gp120 head and gp41 stalk regions. Perhaps most notable was the presence of three splayed legs projecting obliquely from the base of the spike head toward the viral membrane. Subsequently, a second 3D image of SIV spikes, also obtained by cryoET, was published by another group which featured a compact vertical stalk. We now report the cryoET analysis of HIV-1 virion-associated Env spikes using enhanced analytical cryoET procedures. More than 2,000 Env spike volumes were initially selected, aligned, and sorted into structural classes using algorithms that compensate for the “missing wedge” and do not impose any symmetry. The results show varying morphologies between structural classes: some classes showed trimers in the head domains; nearly all showed two or three legs, though unambiguous three-fold symmetry was not observed either in the heads or the legs. Subsequently, clearer evidence of trimeric head domains and three splayed legs emerged when head and leg volumes were independently aligned and classified. These data show that HIV-1, like SIV, also displays the tripod-like leg configuration, and, unexpectedly, shows considerable gp41 leg flexibility/heteromorphology. The tripod-like model for gp41 is consistent with, and helps explain, many of the unique biophysical and immunological features of this region

    The intertropical convergence zone modulates intense hurricane strikes on the western North Atlantic margin

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    © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 21728, doi:10.1038/srep21728Most Atlantic hurricanes form in the Main Development Region between 9°N to 20°N along the northern edge of the Intertropical Convergence Zone (ITCZ). Previous research has suggested that meridional shifts in the ITCZ position on geologic timescales can modulate hurricane activity, but continuous and long-term storm records are needed from multiple sites to assess this hypothesis. Here we present a 3000 year record of intense hurricane strikes in the northern Bahamas (Abaco Island) based on overwash deposits in a coastal sinkhole, which indicates that the ITCZ has likely helped modulate intense hurricane strikes on the western North Atlantic margin on millennial to centennial-scales. The new reconstruction closely matches a previous reconstruction from Puerto Rico, and documents a period of elevated intense hurricane activity on the western North Atlantic margin from 2500 to 1000 years ago when paleo precipitation proxies suggest that the ITCZ occupied a more northern position. Considering that anthropogenic warming is predicted to be focused in the northern hemisphere in the coming century, these results provide a prehistoric analog that an attendant northern ITCZ shift in the future may again return the western North Atlantic margin to an active hurricane interval.This research was supported by NSF Awards: OCE-1519578, OCE-1356708, BCS-1118340

    Orientation and dynamics of transmembrane peptides: the power of simple models

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    In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function

    Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

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    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

    Benthic Fluxes of Oxygen, Ammonium and Nitrate and Coupled-uncoupled Denitrification Rates within Communities of Three Different Primary Producer Growth Forms

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    Inorganic nitrogen and oxygen fluxes together with coupled-uncoupled denitrification were studied in sediments covered by different primary producers (benthic microalgae, the floating macroalga Ulva rigida, and the rooted phanerogam Ruppia cirrhosa). High DIN (Dissolved Inorganic Nitrogen) assimilation rates were measured for all the primary producers and resulted in low denitrification rates, in particular at the Ulva and Ruppia colonised sites. The competition for NH 4 + and NO3 − between phototrophic organisms and nitrifiers-denitrifiers was particularly strong when DIN concentrations in the water column were low. Despite algal uptake denitrification rates were appreciable (>200 µmol N m−2h−1 in the site covered by benthic diatoms due to high availability of NO3 − in the water column and efficient coupling between nitrification and denitrification. In the sites with macrophytes losses of N due to coupled-uncoupled denitrification were negligible compared to assimilation rates. Most of the organic nitrogen pool in the Ulva biomass is probably recycled in the water column while a consistent part of the N stored in Ruppia may be buried in the sediment

    IMG/VR: A database of cultured and uncultured DNA viruses and retroviruses

    Get PDF
    Viruses represent the most abundant life forms on the planet. Recent experimental and computational improvements have led to a dramatic increase in the number of viral genome sequences identified primarily from metagenomic samples. As a result of the expanding catalog of metagenomic viral sequences, there exists a need for a comprehensive computational platform integrating all these sequences with associated metadata and analytical tools. Here we present IMG/VR (https://img.jgi.doe.gov/vr/), the largest publicly available database of 3908 isolate reference DNA viruses with 264 413 computationally identified viral contigs from >6000 ecologically diverse metagenomic samples. Approximately half of the viral contigs are grouped into genetically distinct quasi-species clusters. Microbial hosts are predicted for 20 000 viral sequences, revealing nine microbial phyla previously unreported to be infected by viruses. Viral sequences can be queried using a variety of associated metadata, including habitat type and geographic location of the samples, or taxonomic classification according to hallmark viral genes. IMG/VR has a user-friendly interface that allows users to interrogate all integrated data and interact by comparingwith external sequences, thus serving as an essential resource in the viral genomics community

    Major gradients in putatively nitrifying and non- nitrifying Archaea in the deep North Atlantic

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    International audienceAerobic nitrification of ammonia to nitrite and nitrate is a key process in the oceanic nitrogen cycling mediated by prokaryotes 1 . Besides the two different groups of Bacteria belonging to the beta-and gamma-proteobacteria involved in the first nitrification step, Crenarchaeota have been recently recognized as main drivers of the oxidation of ammonia to nitrite in soil as well as in the ocean as indicated by the dominance of archaeal ammonia monooxygenase (amoA) genes over bacterial amoA 2,3 . Evidence is accumulating that archaeal amoA genes are common in a wide range of marine systems 3-6 . Essentially all these reports focused on surface and mesopelagic (200-1000 m depth) waters where ammonia concentrations are higher than in waters below 1000 m depth. Crenarchaeota are abundant, however, also in the water column below 1000 m depth where ammonia concentrations are extremely low. Here we show, that throughout the North Atlantic, the abundance of archaeal amoA genes decreases drastically from subsurface waters to 4000 m depth and from the subpolar to the equatorial deep waters leading to pronounced vertical and latitudinal gradients in the ratio of archaeal amoA to crenarchaeal 16S rRNA genes. The lack of significant copy numbers of amoA genes in combination with the very low dark carbon dioxide fixation rates in the bathypelagic North Atlantic suggests that the vast majority of the bathypelagic Crenarchaeota are not autotrophic ammonia oxidizers but most likely utilize organic matter, hence live heterotrophically
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