The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Turnover rates of nitrogen stable isotopes in the salt marsh mummichog, Fundulus heteroclitus, following a laboratory diet switch

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Springer-Verlag GmbH for personal use, not for redistribution. The definitive version was published in Oecologia 147 (2006): 391-395, doi:10.1007/s00442-005-0277-z.Nitrogen stable isotopes are frequently used in ecological studies to estimate trophic position and determine movement patterns. Knowledge of tissue-specific turnover and nitrogen discrimination for the study organisms is important for accurate interpretation of isotopic data. We measured δ15 N turnover in liver and muscle tissue in juvenile mummichogs, Fundulus heteroclitus, following a laboratory diet switch. Liver tissue turned over significantly faster than muscle tissue suggesting the potential for a multiple tissue stable isotope approach to study movement and trophic position over different time scales; metabolism contributed significantly to isotopic turnover for both liver and muscle. Nitrogen diet-tissue discrimination was estimated at between 0.0 and 1.2‰ for liver and –1.0 and 0.2‰ for muscle. This is the first experiment to demonstrate a significant variation in δ15 N turnover between liver and muscle tissues in a fish species.This study was funded by NSF LTER grant OCE-9726921

Climate Change Implications for Tidal Marshes and Food Web Linkages to Estuarine and Coastal Nekton

Climate change is altering naturally fluctuating environmental conditions in coastal and estuarine ecosystems across the globe. Departures from long-term averages and ranges of environmental variables are increasingly being observed as directional changes [e.g., rising sea levels, sea surface temperatures (SST)] and less predictable periodic cycles (e.g., Atlantic or Pacific decadal oscillations) and extremes (e.g., coastal flooding, marine heatwaves). Quantifying the short- and long-term impacts of climate change on tidal marsh seascape structure and function for nekton is a critical step toward fisheries conservation and management. The multiple stressor framework provides a promising approach for advancing integrative, cross-disciplinary research on tidal marshes and food web dynamics. It can be used to quantify climate change effects on and interactions between coastal oceans (e.g., SST, ocean currents, waves) and watersheds (e.g., precipitation, river flows), tidal marsh geomorphology (e.g., vegetation structure, elevation capital, sedimentation), and estuarine and coastal nekton (e.g., species distributions, life history adaptations, predator-prey dynamics). However, disentangling the cumulative impacts of multiple interacting stressors on tidal marshes, whether the effects are additive, synergistic, or antagonistic, and the time scales at which they occur, poses a significant research challenge. This perspective highlights the key physical and ecological processes affecting tidal marshes, with an emphasis on the trophic linkages between marsh production and estuarine and coastal nekton, recommended for consideration in future climate change studies. Such studies are urgently needed to understand climate change effects on tidal marshes now and into the future.Full Tex

Human Actions Alter Tidal Marsh Seascapes and the Provision of Ecosystem Services

Tidal marshes are a key component of coastal seascape mosaics that support a suite of socially and economically valuable ecosystem services, including recreational opportunities (e.g., fishing, birdwatching), habitat for fisheries species, improved water quality, and shoreline protection. The capacity for tidal marshes to support these services is, however, threatened by increasingly widespread human impacts that reduce the extent and condition of tidal marshes across multiple spatial scales and that vary substantially through time. Climate change causes species redistribution at continental scales, changes in weather patterns (e.g., rainfall), and a worsening of the effect of coastal squeeze through sea level rise. Simultaneously, the effects of urbanization such as habitat loss, eutrophication, fishing, and the spread of invasive species interact with each other, and with climate change, to fundamentally change the structure and functioning of tidal marshes and their food webs. These changes affect tidal marshes at local scales through changes in plant community composition, complexity, and condition and at regional scales through changes in habitat extent, configuration, and connectivity. However, research into the full effects of these multi-scaled, interactive stressors on ecosystem service provision in tidal marshes is in its infancy and is somewhat geographically restricted. This hinders our capacity to quickly and effectively curb loss and degradation of both tidal marshes and the services they deliver with targeted management actions. We highlight ten priority research questions seeking to quantify the consequences and scales of human impacts on tidal marshes that should be answered to improve management and restoration plans.No Full Tex