Microvesicles: ubiquitous contributors to infection and immunity.

MVs, which can be subgrouped into exosomes, SVs, and OMVs, are secreted by eukaryotic and prokaryotic cells. Many previously inexplicable phenomena can be explained by the existence of these vesicles, as they appear to be important in a wide range of biologic processes, such as intercellular communication and transfer of functional genetic information. In this review, we discuss the immunologic roles of MVs during sterile insult and infectious disease. MVs contribute to clotting initiation, cell recruitment, and neovascularization during wound healing. In the context of pathogen infection, both the host and the pathogen use MVs for communication and defense. MVs are exploited by various viruses to evade the host immune response and contribute to viral spread. Bacteria produce MVs that contain virulence factors that contribute to disease pathology and antibiotic resistance. This review summarizes the role of MVs in the pathology and resolution of disease.

Human coronavirus OC43 nucleocapsid protein binds microRNA 9 and potentiates NF-κB activation.

The human coronavirus OC43 is a major contributor to the common cold worldwide, though due to its low mortality rate, little research has focused on this human pathogen. The nucleocapsid is an essential structural protein with conserved functions across the coronavirus family. While a multitude of studies have examined nucleocapsid function, none have described the effects of OC43 nucleocapsid on the transcription factor NF-κB. We report that the nucleocapsid protein of OC43 causes potentiation of NF-κB activation. This prolonged activation is the direct result of the ability of the nucleocapsid to bind RNA, specifically microRNA 9 (miR-9), which is a negative regulator of NF-κB. This previously undescribed interaction between virus and host is a potential mechanism of immune evasion in RNA viruses.

Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells.

Porcine reproductive and respiratory syndrome (PRRS) is an emerged disease of swine characterized by negligible response of type I IFNs and viral persistence. We show that the PRRSV non-structural protein 1 (Nsp1) is the viral component responsible for modulation of IFN response. Nsp1 blocked dsRNA-induced IRF3 and IFN promoter activities. Nsp1 did not block phosphorylation and nuclear translocation of IRF3 but inhibited IRF3 association with CREB-binding protein (CBP) in the nucleus. While IRF3 was stable, CBP was degraded, and CBP degradation was proteasome-dependent, suggesting that CBP degradation is not due to the protease activity of Nsp1 but an intermediary is involved. Our data suggest that the Nsp1-mediated CBP degradation inhibits the recruitment of CBP for enhanceosome assembly, leading to the block of IFN response. CBP degradation is a novel strategy for viral evasion from the host response, and Nsp1 may form a new class of viral antagonists for IFN modulation.