Search Results (4)

The γ-herpesvirus Epstein–Barr Virus (EBV) establishes lifelong infections in approximately 90% of adults worldwide. Up to 1,000,000 people yearly are estimated to suffer from health conditions attributed to the infection with this virus, such as nasopharyngeal and gastric carcinomas as well as several forms of B, T and NK cell lymphoma. To date, no EBV-specific therapeutic option has reached the market, greatly reducing the survival prognoses of affected patients. Similar to other herpesviruses, EBV encodes for a G protein–coupled receptor (GPCR), BILF1, affecting a multitude of cellular signaling pathways. BILF1 has been identified to promote immune evasion and tumorigenesis, effectively ensuring a life-long persistence of EBV in, and driving detrimental health conditions to its host. This review summarizes the epidemiology of EBV-associated malignancies, their current standard-of-care, EBV-specific therapeutics in development, GPCRs and their druggability, and most importantly consolidates the findings of over 15 years of research on BILF1 in the context of EBV-specific drug development. Taken together, BILF1 constitutes a promising target for the development of novel EBV-specific therapeutics. Full article

Endocytosis is a fundamental process involved in trafficking of various extracellular and transmembrane molecules from the cell surface to its interior. This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. G protein-coupled receptors (GPCRs) constitute a family of receptors with seven transmembrane alpha-helical domains (7TM receptors) expressed at the cell surface, where they regulate physiological and pathological cellular processes. Several herpesviruses encode receptors (vGPCRs) which benefits the virus by avoiding host immune surveillance, supporting viral dissemination, and thereby establishing widespread and lifelong infection, processes where receptor signaling and/or endocytosis seem central. vGPCRs are rising as potential drug targets as exemplified by the cytomegalovirus-encoded receptor US28, where its constitutive internalization has been exploited for selective drug delivery in virus infected cells. Therefore, studying GPCR trafficking is of great importance. This review provides an overview of the current knowledge of endocytic and cell localization properties of vGPCRs and methodological approaches used for studying receptor internalization. Using such novel approaches, we show constitutive internalization of the BILF1 receptor from human and porcine γ-1 herpesviruses and present motifs from the eukaryotic linear motif (ELM) resources with importance for vGPCR endocytosis. Full article

Heterosis is an interesting topic for both breeders and biologists due to its practical importance and scientific significance. Cultivated rice (Oryza sativa L.) consists of two subspecies, indica and japonica, and hybrid rice is the predominant form of indica rice in China. However, the molecular mechanism underlying heterosis in japonica remains unclear. The present study determined the genome sequence and conducted quantitative trait locus (QTL) analysis using backcross recombinant inbred lines (BILs) and BILF₁ lines to uncover the heterosis-related loci for rice yield increase under a japonica genetic background. The BIL population was derived from an admixture variety Habataki and japonica variety Sasanishiki cross to improve the genetic diversity but maintain the genetic background close to japonica. The results showed that heterosis in F₁ mainly involved grain number per panicle. The BILF₁s showed an increase in grain number per panicle but a decrease in plant height compared with the BILs. Genetic analysis then identified eight QTLs for heterosis in the BILF₁s; four QTLs were detected exclusively in the BILF₁ population only, presenting a mode of dominance or super-dominance in the heterozygotes. An additional four loci overlapped with QTLs detected in the BIL population, and we found that Grains Height Date 7 (Ghd7) was correlated in days to heading in both BILs and BILF₁s. The admixture genetic background of Habataki was also determined by subspecies-specific single nucleotide polymorphisms (SNPs). This investigation highlights the importance of high-throughput sequencing to elucidate the molecular mechanism of heterosis and provides useful germplasms for the application of heterosis in japonica rice production. Full article

Epstein-Barr virus (EBV) is characterized by a bipartite life cycle in which latent and lytic stages are alternated. Latency is compatible with long-lasting persistency within the infected host, while lytic expression, preferentially found in oropharyngeal epithelial tissue, is thought to favor host-to-host viral dissemination. The clinical importance of EBV relates to its association with cancer, which we think is mainly a consequence of the latency/persistency mechanisms. However, studies in murine models of tumorigenesis/lymphomagenesis indicate that the lytic cycle also contributes to cancer formation. Indeed, EBV lytic expression is often observed in established cell lines and tumor biopsies. Within the lytic cycle EBV expresses a handful of immunomodulatory (BCRF1, BARF1, BNLF2A, BGLF5 & BILF1) and anti-apoptotic (BHRF1 & BALF1) proteins. In this review, we discuss the evidence supporting an abortive lytic cycle in which these lytic genes are expressed, and how the immunomodulatory mechanisms of EBV and related herpesviruses Kaposi Sarcoma herpesvirus (KSHV) and human cytomegalovirus (HCMV) result in paracrine signals that feed tumor cells. An abortive lytic cycle would reconcile the need of lytic expression for viral tumorigenesis without relaying in a complete cycle that would induce cell lysis to release the newly formed infective viral particles. Full article