Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells

Cell-mediated immunity plays a key role in host control of viral infection. This is exemplified by life-threatening reactivations of e.g. herpesviruses in individuals with impaired T-cell and/or iNKT cell responses. To allow lifelong persistence and virus production in the face of primed immunity, herpesviruses exploit immune evasion strategies. These include a reduction in viral antigen expression during latency and a number of escape mechanisms that target antigen presentation pathways. Given the plethora of foreign antigens expressed in virus-producing cells, herpesviruses are conceivably most vulnerable to elimination by cell-mediated immunity during the replicative phase of infection. Here, we show that a prototypic herpesvirus, Epstein-Barr virus (EBV), encodes a novel, broadly acting immunoevasin, gp150, that is expressed during the late phase of viral replication. In particular, EBV gp150 inhibits antigen presentation by HLA class I, HLA class II, and the non-classical, lipid-presenting CD1d molecules. The mechanism of gp150-mediated T-cell escape does not depend on degradation of the antigen-presenting molecules nor does it require gp150’s cytoplasmic tail. Through its abundant glycosylation, gp150 creates a shield that impedes surface presentation of antigen. This is an unprecedented immune evasion mechanism for herpesviruses. In view of its likely broader target range, gp150 could additionally have an impact beyond escape of T cell activation. Importantly, B cells infected with a gp150-null mutant EBV displayed rescued levels of surface antigen presentation by HLA class I, HLA class II, and CD1d, supporting an important role for iNKT cells next to classical T cells in fighting EBV infection. At the same time, our results indicate that EBV gp150 prolongs the timespan for producing viral offspring at the most vulnerable stage of the viral life cycle

Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

Child Labor in the Small-Scale Gold Mining Industry in Suriname

This study employs a mixed-methods methodology to capture and analyze quantitative and qualitative data on child labor in the small-scale gold mining sector in Suriname. The study addresses issues including, but not limited to, the worst forms of child labor (WFCL) in the gold mining sector, risk factors associated with and pathways into child labor, types of work performed, living and working conditions, and perceptions of the situation from those involved. Using a combination of network analysis, geomapping of the gold sector, and expert interviews, the researchers identified and conducted interviews with 167 child workers drawn from a nonprobability sample of three mining areas (Brokopondo, Meriam, and Sella Creek), and conducted direct observation of mining operations. Findings of the study demonstrate that all child gold miners are engaged in hazardous aspects of mining. Worksite and living conditions are poor and lack the most basic services, such as electricity, toilets, or clean water. At the same time, a distinction is evident between the activities of full-time workers (9.7 percent of those interviewed) and part-time workers (89.3 percent). Full-time workers typically work in the mining pits, where they use sharp tools and dangerous machinery, while the balance are more often engaged in gold panning, which exposes them to the toxic effects of mercury. Gold mining work by children occurs in isolated locations deep within Suriname’s underdeveloped interior; miners come from the impoverished Maroon population, where many households are large families headed by single mothers. Child miners are mostly boys, who are often drawn into the work through the influence of a matrilineal uncle who has the cultural status of a father. Access to high-quality, native-language education is limited; virtually all the children interviewed had a low level of educational achievement partly because they had missed school for work or because they were too physically and mentally exhausted from work to focus on their studies. However, the immediate need to supplement family income or have money of their own, combined with a lack of alternatives, compels children to work in gold mining.ILAB_Child_Labor_in_Suriname.pdf: 617 downloads, before Oct. 1, 2020

Moving Frontiers in the Amazon: Brazilian Small-Scale Gold Miners in Suriname

This article explores the national, local, and personal frontiers that Brazilian small-scale gold miners – called garimpeiros – cross in their quest for gold in the larger Amazon region. Ethnographic research was conducted among garimpeiros and mining service providers in Suriname. In the past three decades, thousands of Brazilian migrants have entered Suriname and consequently affected its society, economy, and culture. It is argued that in the absence of strong state control, these garimpeiros, along with local forest peoples and legal title holders, are traversing the fluctuating boundaries. These boundaries include national borders, customary and legal regulations, technological limitations, and personal livelihood goals. The continuous reformulation of these multiple boundaries drives the development of local mining cultures. Social networks increase the volatility of formal and informal borders, and are the key to these mining cultures as well. The authors conclude that while entering Suriname and its gold mines is relatively easy, financial and conceptual barriers often prevent miners from leaving.Resumen: Fronteras fluctuantes en el Amazonas: los mineros artesanales de oro en SurinameEste artículo explora las fronteras nacionales, locales y personales que cruzan los garimpeiros (como se llama a los mineros brasileños que trabajan explotaciones auríferas a pequeña escala) en su búsqueda de oro en la región amazónica. La investigación etnográfica en que se basa este artículo se realizó entre garimpeiros y proveedores de servicios para la minería en Suriname. En las últimas tres décadas, miles de inmigrantes brasileños han llegado a Suriname y afectado su sociedad, economía y cultura. En el artículo se sostiene que en ausencia de un control estatal fuerte, los garimpeiros, junto con grupos indígenas locales y tenedores de tierra legítimos, cruzan estas fronteras fluctuantes, que incluyen las fronteras nacionales, las regulaciones aduaneras y legales, las limitaciones tecnológicas y los objetivos de supervivencia personal. Esta continua reformulación de fronteras múltiples sostiene el desarrollo de las culturas mineras locales. Las redes sociales aumentan la volatilidad de las fronteras formales e informales, y son de crucial importancia para estas culturas mineras. Los autores concluyen que aunque entrar a Suriname y a sus minas de oro es relativamente fácil, las barreras conceptuales y económicas a menudo impiden que los mineros vuelvan a casa

O Garimpo de ouro na sociedade maroon contemporânea no Suriname

Mineração de ouro em pequena escala é uma das principais atividades econômicas do Suriname. A maior parte do ouro é encontrada no território dos maroons no interior do país. O território ancestral dos Ndjuka, Aluku, Paamaka, Saamaka e Matawai tornaram-se parte de uma disputada área de mineração. Os maroons “alugam” seu território para forasteiros ou trabalham eles próprios com ouro, como donos de máquinas ou trabalhadores em equipes de outros mineiros. Em todo o território maroon o governo nacional fornece concessões a forasteiros, que podem ou não interferem no movimento das populações locais. A mineração ocasiona mudanças ambivalentes no interior. Esse desenvolvimento aumenta o número de questões que queremos sublinhar aqui. Qual é o impacto da chegada de mineiros estrangeiros na comunidade maroon? O envolvimento maroon na mineração contribui para a perda de sua identidade? Quais são os efeitos da participação direta e indireta na mineração de ouro para a cultura maroon

Conceptual Models as Tools for Communication Across Disciplines

This paper suggests that researchers can improve interdisciplinary science through the use of conceptual models as a communication tool. The authors share lessons from a workshop in which interdisciplinary teams of young scientists developed conceptual models of social-ecological systems using data sets and metadata from Long-Term Ecological Research sites across the United States