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Search Results: 1 - 10 of 10580 matches for " Andreas Suhrbier "
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Potent Inhibition of HIV-1 Replication by a Tat Mutant
Luke W. Meredith,Haran Sivakumaran,Lee Major,Andreas Suhrbier,David Harrich
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007769
Abstract: Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection.
Circulating Heat Shock Protein 60 Levels Are Elevated in HIV Patients and Are Reduced by Anti-Retroviral Therapy
Itaru Anraku, Reena Rajasuriar, Caroline Dobbin, Richard Brown, Sharon R. Lewin, Andreas Suhrbier
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045291
Abstract: Circulating heat shock protein 60 (Hsp60) and heat shock protein 10 (Hsp10) have been associated with pro- and anti-inflammatory activity, respectively. To determine whether these heat shock proteins might be associated with the immune activation seen in HIV-infected patients, the plasma levels of Hsp60 and Hsp10 were determined in a cohort of 20 HIV-infected patients before and after effective combination anti-retroviral therapy (cART). We show for the first time that circulating Hsp60 levels are elevated in HIV-infected patients, with levels significantly reduced after cART, but still higher than those in HIV-negative individuals. Hsp60 levels correlated significantly with viral load, CD4 counts, and circulating soluble CD14 and lipopolysaccharide levels. No differences or correlations were seen for Hsp10 levels. Elevated circulating Hsp60 may contribute to the immune dysfunction and non-AIDS clinical events seen in HIV-infected patients.
Ticks Associated with Macquarie Island Penguins Carry Arboviruses from Four Genera
Lee Major, May La Linn, Robert W. Slade, Wayne A. Schroder, Alex D. Hyatt, Joy Gardner, Jeff Cowley, Andreas Suhrbier
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004375
Abstract: Macquarie Island, a small subantarctic island, is home to rockhopper, royal and king penguins, which are often infested with the globally distributed seabird tick, Ixodes uriae. A flavivirus, an orbivirus, a phlebovirus, and a nairovirus were isolated from these ticks and partial sequences obtained. The flavivirus was nearly identical to Gadgets Gully virus, isolated some 30 year previously, illustrating the remarkable genetic stability of this virus. The nearest relative to the orbivirus (for which we propose the name Sandy Bay virus) was the Scottish Broadhaven virus, and provided only the second available sequences from the Great Island orbivirus serogroup. The phlebovirus (for which we propose the name Catch-me-cave virus) and the previously isolated Precarious Point virus were distinct but related, with both showing homology with the Finnish Uukuniemi virus. These penguin viruses provided the second and third available sequences for the Uukuniemi group of phleboviruses. The nairovirus (for which we propose the name Finch Creek virus) was shown to be related to the North American Tillamook virus, the Asian Hazara virus and Nairobi sheep disease virus. Macquarie Island penguins thus harbour arboviruses from at least four of the seven arbovirus-containing genera, with related viruses often found in the northern hemisphere.
Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells
Stefan W. Metz,Joy Gardner,Corinne Geertsema,Thuy T. Le,Lucas Goh,Just M. Vlak,Andreas Suhrbier,Gorben P. Pijlman
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002124
Abstract: The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs) in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 μg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Réunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.
Induction of SerpinB2 and Th1/Th2 Modulation by SerpinB2 during Lentiviral Infections In Vivo
Lee D. Major, Thomas S. Partridge, Joy Gardner, Stephen J. Kent, Robert de Rose, Andreas Suhrbier, Wayne A. Schroder
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057343
Abstract: SerpinB2, also known as plasminogen activator inhibitor type 2, is a major product of activated monocytes/macrophages and is often strongly induced during infection and inflammation; however, its physiological function remains somewhat elusive. Herein we show that SerpinB2 is induced in peripheral blood mononuclear cells following infection of pigtail macaques with CCR5-utilizing (macrophage-tropic) SIVmac239, but not the rapidly pathogenic CXCR4-utilizing (T cell-tropic) SHIVmn229. To investigate the role of SerpinB2 in lentiviral infections, SerpinB2?/? mice were infected with EcoHIV, a chimeric HIV in which HIV gp120 has been replaced with gp80 from ecotropic murine leukemia virus. EcoHIV infected SerpinB2?/? mice produced significantly lower anti-gag IgG1 antibody titres than infected SerpinB2+/+ mice, and showed slightly delayed clearance of EcoHIV. Analyses of published microarray studies showed significantly higher levels of SerpinB2 mRNA in monocytes from HIV-1 infected patients when compared with uninfected controls, as well as a significant negative correlation between SerpinB2 and T-bet mRNA levels in peripheral blood mononuclear cells. These data illustrate that SerpinB2 can be induced by lentiviral infection in vivo and support the emerging notion that a physiological role of SerpinB2 is modulation of Th1/Th2 responses.
La mezcla justa. El trayecto de la coca a través de los objetos culturales. Interpretación de un dibujo de Alfredo Fontes (Tukano1/ amazonia noroccidental)
Mona Birgit Suhrbier
Boletín de Antropología , 2004,
Abstract: La cultura material de los grupos indígenas de América del Sur ocupa un lugar importante en las colecciones de los museos de Europa. Pese a ello, cestos, vasijas, alhajas, armas, máscaras y muchos otros objetos de uso cotidiano y ritual están, con frecuencia, sólo rudimentariamente documentados y descritos. Son raras las ocasiones en que se da la oportunidad de documentar posteriormente, en el marco de estadías de investigación de campo, objetos que ya se encuentran en los museos. Una posibilidad de adquirir mayor conocimiento sobre la cultura material es la interpretación del arte, pues los objetos de pintores y dibujantes indígenas de las respectivas culturas tienen, por lo general, un papel importante entre los múltiples espacios de la vida indígena. Los artistas, sin embargo, no pretenden realzar la utilidad práctica de los objetos de uso, sino que realzan tales objetos como partes de un orden más amplio y simbólicamente estructurado, en el cual también tienen importancia el concepto de la humanidad y la idea de una vida buena. En el texto se realiza un análisis formal del dibujo Utensilios para la producción de Ipadu (1999) de Alfredo Miguel Fontes, tukano (Brasil), y se relaciona con lo que se sabe sobre los objetos representados en este dibujo.
A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease
Suganya Selvarajah,Nicole R. Sexton,Kristen M. Kahle,Rachel H. Fong,Kimberly-Anne Mattia,Joy Gardner,Kai Lu,Nathan M. Liss,Beatriz Salvador,David F. Tucker,Trevor Barnes,Manu Mabila,Xiangdong Zhou,Giada Rossini,Joseph B. Rucker,David Avram Sanders,Andreas Suhrbier,Vittorio Sambri,Alain Michault,Marcus O. Muench,Benjamin J. Doranz,Graham Simmons
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002423
Abstract: The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.
Multiple Immune Factors Are Involved in Controlling Acute and Chronic Chikungunya Virus Infection
Yee Suan Poo,Penny A. Rudd,Joy Gardner,Jane A. C. Wilson,Thibaut Larcher,Marie-Anne Colle,Thuy T. Le,Helder I. Nakaya,David Warrilow,Richard Allcock,Helle Bielefeldt-Ohmann,Wayne A. Schroder,Alexander A. Khromykh,José A. Lopez,Andreas Suhrbier
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003354
Abstract: The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.
Economic Growth and a Low Carbon Economy―Does the Earth Suffer from an “Easter Island Syndrome”?  [PDF]
Andreas Oberheitmann
Low Carbon Economy (LCE) , 2011, DOI: 10.4236/lce.2011.24024
Abstract: The history of the Eastern Islands in the Pacific with an increasing over-utilization of natural resources reminds us of the mistakes modern societies are making and the question is obvious whether the Earth is suffering from an Eastern Islands Syndrome, in other words whether the egoism inherent in humans long-term might have fatal consequences for our species homo sapiens. Climate research identified two important phenomena, which should remind us of the Easter Islands: feedbacks and tipping points, i.e. self-accelerating phenomena of global warming and reaching irreversible points of climate change. Only a quick worldwide return to a low carbon economy is able to stabilize global warming on a bearable level. Both, Annex-I countries and Non-Annex-I countries have to contribute to reaching this goal taking their historical, current and future responsibilities into account. A post Kyoto regime based on cumulative per-capita CO2-emission rights and a international emission trading could provide for incentives to achieve a low carbon economy, especially for newly industrialized countries.
Development of a Low Carbon Economy in Wuxi City  [PDF]
Andreas Oberheitmann
American Journal of Climate Change (AJCC) , 2012, DOI: 10.4236/ajcc.2012.12007
Abstract: The development of a Low Carbon Economy is a vital instrument to encounter climate change and take into account the growing challenges of an increasing urbanization in China. Wuxi City in East China’s Jiangsu Province is starting to implement a Low Carbon City Plan for safeguarding a sustainable development of the city until 2020 and beyond. This paper aims at estimating the impact of the Low Carbon City plan for Wuxi’s energy demand and CO2-emissions until 2050. Using an econometric energy supply and demand model to estimate and forecast the Wuxi energy and CO2-balance aggregates until 2050, it compares a scenario without specific Low Carbon City measures to reduce sectoral CO2-intensities to a Low Carbon scenario implementing these measures according to the Low Carbon City Plan until 2020 and beyond. The decomposition of the Kaya-identity reveals that the increase of per capita income has the largest impact on the growth of CO2-emissions and the decrease of energy intensity of Gross Value Added the largest impact on the reduction of CO2-emissions in Wuxi. A decrease of population and CO2-intensity of Primary energy supply only have average contributions. The decrease of energy intensity of Gross Value Added is due to energy efficiency gains in the single economic sectors, but to a large extent due to structural changes of the economy away from energy intensive sectors such as iron and steel, chemical industry or cement industry towards the energy extensive service sectors. A growing residential sector also reduces the industrial share of energy demand. Only following the assumed national trend with a shift from CO2-intensive industries to a CO2-extensive service economy, the Low Carbon goal of a 50% reduction of CO2-intensity of Gross Value Added compared to 2005 cannot be reached in Wuxi. Specific sectoral CO2 -intensity goals have to be successfully observed by the economic sectors in Wuxi, especially by the industry. The promotion of combined heat and power generation also has to contribute to the specific activities in Wuxi.
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