CircRNA_0050463 promotes influenza A virus replication by sponging miR-33b-5p to regulate EEF1A1.

Circular RNAs (circRNAs), a new class of widely expressed endogenous regulatory RNAs, are characterized by a covalently closed loop structure without a 5' cap or 3' tail. Increasing numbers of studies have shown that circRNAs play important roles in diverse physiological and pathological processes, including the dynamic interactions between viruses and hosts. However, their multifaceted roles in cellular responses to influenza A virus (IAV) infection remain largely unknown. Here, we analyzed the expression of circ_0050463, which is predominantly localized in cytoplasm, in response to IAV infection. Knockdown of circ_0050463 with siRNA in A549 cells inhibited IAV replication. In addition, the activation of nuclear factor κB (NF-κB) was involved in IAV-induced circ_0050463 expression, as revealed by assay using a NF-Kb inhibitor (Bay 11-7082). By performing biotin-labeled RNA pull-down and luciferase reporter assay, we demonstrated that circ_0050463 functioned as an endogenous microRNA-33b-5p sponge to sequester and inhibit miR-33b-5p activity, resulting in increased eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) expression with subsequent facilitation of IAV replication. Taken together, the results of our study indicate that the circ_0050463 promotes IAV replication via miR-33b-5p/EEF1A1 axis, thus providing evidence for the host circRNAs utilized by viruses to support their replication.

Proteomics in Influenza Research: The Emerging Role of Posttranslational Modifications.

Influenza viruses continue evolving and have the ability to cause a global pandemic, so it is very important to elucidate its pathogenesis and find new treatment methods. In recent years, proteomics has made important contributions to describing the dynamic interaction between influenza viruses and their hosts, especially in posttranslational regulation of a variety of key biological processes. Protein posttranslational modifications (PTMs) increase the diversity of functionality of the organismal proteome and affect almost all aspects of pathogen biology, primarily by regulating the structure, function, and localization of the modified proteins. Considerable technical achievements in mass spectrometry-based proteomics have been made in a large number of proteome-wide surveys of PTMs in many different organisms. Herein we specifically focus on the proteomic studies regarding a variety of PTMs that occur in both the influenza viruses, mainly influenza A viruses (IAVs), and their hosts, including phosphorylation, ubiquitination and ubiquitin-like modification, glycosylation, methylation, acetylation, and some types of acylation. Integration of these data sets provides a unique scenery of the global regulation and interplay of different PTMs during the interaction between IAVs and their hosts. Various techniques used to globally profiling these PTMs, mostly MS-based approaches, are discussed regarding their increasing roles in mechanical regulation of interaction between influenza viruses and their hosts.

Administration of Exogenous Progesterone Protects Against Brucella abortus Infection-Induced Inflammation in Pregnant Mice.

Progesterone has been recognized as essential for the establishment and maintenance of pregnancy, and is typically known as an immunosuppressive agent. However, its effects on mediating Brucella infection-induced inflammation have not been evaluated. Here we demonstrated that Brucella abortus infection inhibits progesterone levels in the pregnant mouse by suppressing the production of progesterone by placenta. Progesterone treatment significantly reduced the secretion of inflammatory cytokines in serum, macrophages, and trophoblasts of B. abortus-infected mice, leading to decreased placentitis and enhancing the pup viability. Mechanistically, this decreased inflammatory response results from inhibition of NF-kB activation by progesterone. Moreover, progesterone treatment suppresses B. abortus growth within trophoblasts associated with an inability of bacteria to escape the late endosome compartment in vitro. Collectively, our data illustrate that progesterone treatment might be useful therapeutically in protection against placentitis or abortion caused by B. abortus infection.