Gammaherpesvirus-mediated repression reveals EWSR1 to be a negative regulator of B cell responses.

The germinal center (GC) plays a central role in the generation of antigen-specific B cells and antibodies. Tight regulation of the GC is essential due to the inherent risks of tumorigenesis and autoimmunity posed by inappropriate GC B cell processes. Gammaherpesviruses such as Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68) utilize numerous armaments to drive infected naïve B cells, independent of antigen, through GC reactions to expand the latently infected B cell population and establish a stable latency reservoir. We previously demonstrated that the MHV68 microRNA (miRNA) mghv-miR-M1-7-5p represses host EWSR1 (Ewing sarcoma breakpoint region 1) to promote B cell infection. EWSR1 is a transcription and splicing regulator that is recognized for its involvement as a fusion protein in Ewing sarcoma. A function for EWSR1 in B cell responses has not been previously reported. Here, we demonstrate that 1) B cell-specific deletion of EWSR1 had no effect on generation of mature B cell subsets or basal immunoglobulin levels in naïve mice, 2) repression or ablation of EWSR1 in B cells promoted expansion of MHV68 latently infected GC B cells, and 3) B cell-specific deletion of EWSR1 during a normal immune response to nonviral antigen resulted in significantly elevated numbers of antigen-specific GC B cells, plasma cells, and circulating antibodies. Notably, EWSR1 deficiency did not affect the proliferation or survival of GC B cells but instead resulted in the generation of increased numbers of precursor GC B cells. Cumulatively, these findings demonstrate that EWSR1 is a negative regulator of B cell responses.

Impact of the COVID-19 Pandemic on Disordered Eating Behavior: Qualitative Analysis of Social Media Posts.

BACKGROUND: A growing body of evidence is suggesting a significant association between the COVID-19 pandemic and population-level mental health. Study findings suggest that individuals with a lifetime history of disordered eating behavior may be negatively affected by COVID-19-related anxiety, and prevention measures may disrupt daily functioning and limit access to treatment. However, data describing the influence of the COVID-19 pandemic on disordered eating behaviors are limited, and most findings focus on individuals in treatment settings. OBJECTIVE: The aim of this study is to characterize the experiences of Reddit users worldwide who post in eating disorder (ED)-related discussion forums describing the influence of the COVID-19 pandemic on their overall mental health and disordered eating behavior. METHODS: Data were collected from popular subreddits acknowledging EDs as their primary discussion topic. Unique discussion posts dated from January 1 to May 31, 2020 that referenced the COVID-19 pandemic were extracted and evaluated using inductive, thematic data analysis. RESULTS: Six primary themes were identified: change in ED symptoms, change in exercise routine, impact of quarantine on daily life, emotional well-being, help-seeking behavior, and associated risks and health outcomes. The majority of users reported that the COVID-19 pandemic and associated public health prevention measures negatively impacted their psychiatric health and contributed to increased disordered eating behaviors. Feelings of isolation, frustration, and anxiety were common. Many individuals used Reddit forums to share personal experiences, seek advice, and offer shared accountability. CONCLUSIONS: Reddit discussion forums have provided a therapeutic community for individuals to share experiences and provide support for peers with ED during a period of increased psychiatric distress. Future research is needed to assess the impact of the COVID-19 pandemic on disordered eating behavior and to evaluate the role of social media discussion forums in mental health treatment, especially during periods of limited treatment access.