Epstein-Barr Virus LMP2A Reduces Hyperactivation Induced by LMP1 to Restore Normal B Cell Phenotype in Transgenic Mice

Epstein-Barr virus (EBV) latently infects most of the human population and is strongly associated with lymphoproliferative disorders. EBV encodes several latency proteins affecting B cell proliferation and survival, including latent membrane protein 2A (LMP2A) and the EBV oncoprotein LMP1. LMP1 and LMP2A signaling mimics CD40 and BCR signaling, respectively, and has been proposed to alter B cell functions including the ability of latently-infected B cells to access and transit the germinal center. In addition, several studies suggested a role for LMP2A modulation of LMP1 signaling in cell lines by alteration of TRAFs, signaling molecules used by LMP1. In this study, we investigated whether LMP1 and LMP2A co-expression in a transgenic mouse model alters B cell maturation and the response to antigen, and whether LMP2A modulates LMP1 function. Naïve LMP1/2A mice had similar lymphocyte populations and antibody production by flow cytometry and ELISA compared to controls. In the response to antigen, LMP2A expression in LMP1/2A animals rescued the impairment in germinal center generation promoted by LMP1. LMP1/2A animals produced high-affinity, class-switched antibody and plasma cells at levels similar to controls. In vitro, LMP1 upregulated activation markers and promoted B cell hyperproliferation, and co-expression of LMP2A restored a wild-type phenotype. By RT-PCR and immunoblot, LMP1 B cells demonstrated TRAF2 levels four-fold higher than non-transgenic controls, and co-expression of LMP2A restored TRAF2 levels to wild-type levels. No difference in TRAF3 levels was detected. While modulation of other TRAF family members remains to be assessed, normalization of the LMP1-induced B cell phenotype through LMP2A modulation of TRAF2 may be a pathway by which LMP2A controls B cell function. These findings identify an advance in the understanding of how Epstein-Barr virus can access the germinal center in vivo, a site critical for both the genesis of immunological memory and of virus-associated tumors

Measuring the Enabling Environment of Civil Society: A Global Capability Index

During the last two decades, there have been various attempts at measuring and assessing the health of civil society. Some have focused almost exclusively on „counting‟ the nonprofit while others have assessed the strength of nongovernmental organizations. Yet, these sectors are just a small part of a much larger environment. Moreover, they are the result of Western conceptualizations of civil society, thus not very helpful to understand civic participation in non-Western settings. Taking stock of these fundamental issues, this article presents the conceptual framework and methodology of a new global index to measure the „enabling environment‟ of civil society, rather than its forms and institutional contours. Given the inherent diversity of civil societies worldwide, which defies any attempt at developing predetermined definitions, understanding the conditions that support civic participation becomes the most important objective for those interested in promoting a strong civil society arena. The index was launched by CIVICUS in late 2013 with the name of Enabling Environment Index and covers 200 countries and territories, making it the most ambitious attempt ever made at measuring civil society worldwide.http://link.springer.com/journal/112662016-04-30hb201