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Search Results: 1 - 10 of 541 matches for " Bastian Grewe "
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The HIV-1 Rev Protein Enhances Encapsidation of Unspliced and Spliced, RRE-Containing Lentiviral Vector RNA
Bastian Grewe, Katrin Ehrhardt, Bianca Hoffmann, Maik Blissenbach, Sabine Brandt, Klaus überla
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048688
Abstract: Background During the RNA encapsidation process of human immunodeficiency virus (HIV) viral genomic, unspliced RNA (gRNA) is preferentially incorporated into assembling virions. However, a certain amount of spliced viral transcripts can also be detected in viral particles. Recently, we observed that nuclear export of HIV and lentiviral vector gRNA by Rev is required for efficient encapsidation. Since singly-spliced HIV transcripts also contain the Rev-response element (RRE), we investigated if the encapsidation efficiency of RRE-containing spliced HIV-vector transcripts is also increased by the viral Rev protein. Findings Starting with a lentiviral vector imitating the splicing pattern of HIV, we constructed vectors that express an unspliced transcript either identical in sequence to the singly-spliced or the fully-spliced RNA of the parental construct. After transfection of the different lentiviral vectors cytoplasmic and virion-associated RNA levels and vector titers were determined in the presence and absence of Rev. Rev enhanced the infectious titer of vectors containing an RRE 6 to 37-fold. Furthermore, Rev strongly increased encapsidation efficiencies of all RRE-containing transcripts up to 200-fold. However, a good correlation between encapsidation efficiency and lentiviral vector titer could only be observed for the gRNA. The infectious titer of the vector encoding the fully-spliced RNA without RRE as well as the encapsidation efficiency of all transcripts lacking the RRE was not influenced by Rev. Interestingly, the splicing process itself did not seem to interfere with packaging, since the encapsidation efficiencies of the same RNA expressed either by splicing or as an unspliced transcript did not differ significantly. Conclusions Rev-mediated nuclear export enhances the encapsidation efficiency of RRE-containing lentiviral vector RNAs independently of whether they have been spliced or not.
Rev Proteins of Human and Simian Immunodeficiency Virus Enhance RNA Encapsidation
Sabine Brandt equal contributor,Maik Bli?enbach equal contributor,Bastian Grewe,Rebecca Konietzny,Thomas Grunwald,Klaus überla
PLOS Pathogens , 2007, DOI: 10.1371/journal.ppat.0030054
Abstract: The main function attributed to the Rev proteins of immunodeficiency viruses is the shuttling of viral RNAs containing the Rev responsive element (RRE) via the CRM-1 export pathway from the nucleus to the cytoplasm. This restricts expression of structural proteins to the late phase of the lentiviral replication cycle. Using Rev-independent gag-pol expression plasmids of HIV-1 and simian immunodeficiency virus and lentiviral vector constructs, we have observed that HIV-1 and simian immunodeficiency virus Rev enhanced RNA encapsidation 20- to 70-fold, correlating well with the effect of Rev on vector titers. In contrast, cytoplasmic vector RNA levels were only marginally affected by Rev. Binding of Rev to the RRE or to a heterologous RNA element was required for Rev-mediated enhancement of RNA encapsidation. In addition to specific interactions of nucleocapsid with the packaging signal at the 5′ end of the genome, the Rev/RRE system provides a second mechanism contributing to preferential encapsidation of genomic lentiviral RNA.
Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
Donatien Kamdem Toukam, Matthias Tenbusch, Alexander Stang, Vladimir Temchura, Michael Storcksdieck genannt Bonsmann, Bastian Grewe, Stefanie Koch, Andreas Meyerhans, Godwin Nchinda, Lazare Kaptue, Klaus überla
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038068
Abstract: Although human immunodeficiency type 1 (HIV-1) infection induces strong antibody responses to the viral envelope glycoprotein (Env) only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10) target the short and hidden membrane proximal external region (MPER) of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP). Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined.
A generalized tagging method
V. Grewe
Geoscientific Model Development (GMD) & Discussions (GMDD) , 2013, DOI: 10.5194/gmd-6-247-2013
Abstract: The understanding of causes of changes in climate-chemistry simulations is an important, but often challenging task. In atmospheric chemistry, one approach is to tag species according to their origin (e.g. emission categories) and to inherit these tags to other species during subsequent reactions. This concept was recently employed to calculate the contribution of atmospheric processes to temperature. Here a new concept for tagging any state variable is presented. This generalized tagging method results from a sensitivity analysis of the individual forcing terms of the right hand side of the governing differential equations. In a couple of examples, the consistency with previous approaches and the synergy by using different analysis techniques are shown. Since the method is based on a ratio describing relative sensitivities, singularities occur where the method is not applicable. For some applications, such as in atmospheric chemistry, these singularities can easily be removed. However, one theoretical example is given, where this method is not applicable at all.
A new method to diagnose the contribution of anthropogenic activities to temperature: temperature tagging
V. Grewe
Geoscientific Model Development (GMD) & Discussions (GMDD) , 2013, DOI: 10.5194/gmd-6-417-2013
Abstract: This study presents a new methodology, called temperature tagging. It keeps track of the contributions of individual processes to temperature within a climate model simulation. As a first step and as a test bed, a simple box climate model is regarded. The model consists of an atmosphere, which absorbs and emits radiation, and of a surface, which reflects, absorbs and emits radiation. The tagging methodology is used to investigate the impact of the atmosphere on surface temperature. Four processes are investigated in more detail and their contribution to the surface temperature quantified: (i) shortwave influx and shortwave atmospheric absorption ("sw"), (ii) longwave atmospheric absorption due to non-CO2 greenhouse gases ("nC"), (iii) due to a base case CO2 concentration ("bC"), and (iv) due to an enhanced CO2 concentration ("eC"). The differential equation for the temperature in the box climate model is decomposed into four equations for the tagged temperatures. This method is applied to investigate the contribution of longwave absorption to the surface temperature (greenhouse effect), which is calculated to be 68 K. This estimate contrasts an alternative calculation of the greenhouse effect of slightly more than 30 K based on the difference of the surface temperature with and without an atmosphere. The difference of the two estimates is due to a shortwave cooling effect and a reduced contribution of the shortwave to the total downward flux: the shortwave absorption of the atmosphere results in a reduced net shortwave flux at the surface of 192 W m 2, leading to a cooling of the surface by 14 K. Introducing an atmosphere results in a downward longwave flux at the surface due to atmospheric absorption of 189 W m 2, which roughly equals the net shortwave flux of 192 W m 2. This longwave flux is a result of both the radiation due to atmospheric temperatures and its longwave absorption. Hence the longwave absorption roughly accounts for 91 W m 2 out of a total of 381 W m 2 (roughly 25%) and therefore accounts for a temperature change of 68 K. In a second experiment, the CO2 concentration is doubled, which leads to an increase in surface temperature of 1.2 K, resulting from a temperature increase due to CO2 of 1.9 K, due to non-CO2 greenhouse gases of 0.6 K and a cooling of 1.3 K due to a reduced importance of the solar heating for the surface and atmospheric temperatures. These two experiments show the feasibility of temperature tagging and its potential as a diagnostic for climate simulations.
The origin of ozone
V. Grewe
Atmospheric Chemistry and Physics (ACP) & Discussions (ACPD) , 2006,
Abstract: Highest atmospheric ozone production rates can be found at around 30 km in the tropical stratosphere, leading to ozone mixing ratios of about 10 ppmv. Those stratospheric air masses are then transported to extra-tropical latitudes via the Brewer-Dobson circulation. This is considered the main mechanism to generate mid- and high latitude ozone. By applying the climate-chemistry models E39/C and MAECHAM4/CHEM, this view is investigated in more detail. The origin of ozone in the troposphere and stratosphere is analysed, by incorporating a diagnostics ("marked ozone origin tracers") into the models, which allows to identify the origin of ozone. In most regions the simulated local ozone concentration is dominated by local ozone production, i.e. less than 50% of the ozone at higher latitudes of the stratosphere is produced in the tropics, which conflicts with the idea that the tropics are the global source for stratospheric ozone. Although episodic stratospheric intrusions occur basically everywhere, the main ozone stratosphere-to-troposphere exchange is connected to exchange processes at the sub-tropical jet-stream. The simulated tropospheric influx of ozone amounts to 420 Tg per year, and originates in the Northern Hemisphere from the extra-tropical stratosphere, whereas in the Southern Hemisphere a re-circulation of tropical tropospheric ozone contributes most to the influx of ozone into the troposphere. In the model E39/C, the upper troposphere of both hemispheres is clearly dominated by tropical tropospheric ozone (40%–50%) except for northern summer hemisphere, where the tropospheric contribution (from the tropics as well as from the Northern Hemisphere) does not exceed 20%.
Technical Note: A diagnostic for ozone contributions of various NOx emissions in multi-decadal chemistry-climate model simulations
V. Grewe
Atmospheric Chemistry and Physics (ACP) & Discussions (ACPD) , 2004,
Abstract: Nitrogen oxide (NOx=NO+NO2) emissions from various sources contribute to the ozone budget. The identification of these contributions is important, e.g. for the assessment of emissions from traffic. The non-linear character of ozone chemistry complicates the online diagnosis during multi-decadal chemistry-climate simulations. A methodology is suggested, which is efficient enough to be incorporated in multi-decadal simulations. Eight types of NOx emissions are included in the model. For each a NOy (=all N components, except N2 and N2O) tracer and an ozone tracer is included in the model, which experience the same emissions and loss processes like the online chemistry fields. To calculate the ozone changes caused by an individual NOx emission, the assumption is made that the NOx relative contributions from various sources are identical to the NOy relative contributions. To evaluate this method each NOx emission has been increased by 5% and a detailed error analysis is given. In the regions of the main impact of individual sources the potential error of the calculated contribution is significantly smaller than the contribution. Moreover, the changes caused by an increase of the emissions of 5% were detected with a higher accuracy than the potential error of the absolute contribution.
A new method to diagnose the contribution of anthropogenic activities to temperature: temperature tagging
V. Grewe
Geoscientific Model Development Discussions , 2012, DOI: 10.5194/gmdd-5-3183-2012
Abstract: This study presents a new methodology, called temperature tagging. It keeps track of the contributions of individual processes to temperature within a climate model simulation. As a first step and as a test bed a simple box climate model is regarded. The model consists of an atmosphere, which absorbs and emits radiation and of a surface, which reflects, absorbs and emits radiation. The tagging methodology is used to investigate the impact of the atmosphere on surface temperature. Four processes are investigated in more detail and their contribution to the surface temperature quantified: (i) shortwave influx and shortwave atmospheric absorption ("sw"), (ii) longwave atmospheric absorption due to non-CO2 greenhouse gases ("nC"), (iii) due to a base case CO2 concentration ("bC"), and (iv) due to an enhanced CO2 concentration ("eC"). The differential equation for the temperature in the box climate model is decomposed into four equations for the tagged temperatures. This method is applied to investigate the contribution of longwave absorption to the surface temperature (greenhouse effect), which is calculated to be 68 K. This estimate contrasts an alternative calculation of the greenhouse effect of slightly more than 30 K based on the difference of the surface temperature with and without an atmosphere. The difference of the two estimates is due to a shortwave cooling effect and a reduced contribution of the shortwave to the total downward flux: The shortwave absorption of the atmosphere results in a reduced net shortwave flux at the surface of 192 W m 2, leading to a cooling of the surface by 14 K. Introducing an atmosphere results in a downward longwave flux at the surface due to atmospheric absorption of 189 W m 2, which roughly equals the net shortwave flux of 192 W m 2. This longwave flux is a result of both, the radiation due to atmospheric temperatures and its longwave absorption. Hence the longwave absorption roughly accounts for 91 W m 2 out of a total of 381 W m 2 (roughly 25%) and therefore accounts for a temperature of 68 K. In a second experiment, the CO2 concentration is doubled, which leads to an increase in surface temperature of 1.2 K, resulting from an temperature increase due to CO2 of 1.9 K, due to non-CO2 greenhouse gases of 0.6 K and a cooling of 1.3 K due to a reduced importance of the solar heating for the surface and atmospheric temperatures. These two experiments show the feasibility of temperature tagging and its potential as a diagnostic for climate simulations.
A generalized tagging method
V. Grewe
Geoscientific Model Development Discussions , 2012, DOI: 10.5194/gmdd-5-3311-2012
Abstract: The understanding of causes of changes in climate-chemistry simulations is an important, but often challenging task. In atmospheric chemistry, one approach is to tag species according to their origin (e.g. emission categories) and to inherit these tags to other species during subsequent reactions. This concept was recently employed to calculate the contribution of atmospheric processes to temperature. Here a new concept for tagging any state variable is presented. This generalized tagging method results from a sensitivity analysis of the forcing terms of the right hand side of the governing differential equations. In a couple of examples, the consistency with previous approaches is shown. Since the method is based on a ratio describing relative sensitivities, singularities occur where the method is not applicable. For some applications, like in atmospheric chemistry, these singularities can easily be removed. However, one theoretical example is given, where this method is not applicable at all.
Technical Note: A diagnostic for ozone contributions of various NOx emissions in multi-decadal chemistry-climate model simulations
V. Grewe
Atmospheric Chemistry and Physics Discussions , 2004,
Abstract: Nitrogen oxide (NOx=NO+NO2) emissions from various sources contribute to the ozone budget. The identification of these contributions is important, e.g. for the assessment of emissions from traffic. The non-linear character of ozone chemistry complicates the online diagnosis during multi-decadal chemistry-climate simulations. A methodology is suggested, which is efficient enough to be incorporated in multi-decadal simulations. Eight types of NOx emissions are included in the model. For each a NOy (=all N components, except N2 and N2O) tracer and an ozone tracer is included in the model, which experience the same emissions and loss processes like the online chemistry fields. To calculate the ozone changes caused by an individual NOx emission, the assumption is made that the NOx contributions from various sources are identical to the NOy contributions. To evaluate this method each NOx emission has been increased by 5% and a detailed error analysis is given. In the regions of the main impact of individual sources the potential error of the calculated contribution is significantly smaller than the contribution. Moreover, the changes caused by an increase of the emissions of 5% were detected with a higher accuracy than the potential errror of the absolut contribution.
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