RESUMO
BACKGROUND: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. RESULTS: In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. CONCLUSIONS: This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.
Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Genoma Humano , Antígenos Nucleares do Vírus Epstein-Barr/genética , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Proteínas Virais/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Food insecurity and obesity are increasing both globally and in the UK. In this review we systematically assess the lived experiences of people with obesity who are food insecure and often turn to food banks. METHODS: We systematically searched electronic databases from January 2007 until October 2022. Data from eligible studies were extracted and the studies assessed for quality. Thematic analysis and narrative synthesis approach was used to analyse the extracted data. RESULTS: Six themes were identified among 25 included studies, including: the financial cost of food; psychological aspects related to food insecurity; geographical access and the food environment; food practices in the home; experience of food assistance; and parental-child relationships. The cost of healthy food and psychological factors were identified as key driving factors of the relationship between food insecurity and obesity. Psychological factors such as depression, low self-esteem and stress played an important part in the lived experience of people with obesity and food insecurity. CONCLUSION: The food environment provides context in which food decisions are made, therefore, systems change is necessary to ensure families can afford the food that enables a healthy diet. For clinicians, identification, and attention to the impact of food insecurity on people with obesity are important.