Cytosolic Sensing of Viruses.
ABSTRACT Cells are equipped with mechanisms that allow them to rapidly detect and respond to viruses. These defense mechanisms rely partly on receptors that monitor the cytosol for the presence of atypical nucleic acids associated with virus infection. RIG-I-like receptors detect RNA molecules that are absent from the uninfected host. DNA receptors alert the cell to the abnormal presence of that nucleic acid in the cytosol. Signaling by RNA and DNA receptors results in the induction of restriction factors that prevent virus replication and establish cell-intrinsic antiviral immunity. In light of these formidable obstacles, viruses have evolved mechanisms of evasion, masking nucleic acid structures recognized by the host, sequestering themselves away from the cytosol or targeting host sensors, and signaling adaptors for deactivation or degradation. Here, we detail recent advances in the molecular understanding of cytosolic nucleic acid detection and its evasion by viruses.
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ABSTRACT: Viral triggering of the innate immune response in infected cells aims at delaying viral replication and prevents tissue spreading. Viral replication is delayed by host protein synthesis inhibition and infected cell apoptosis on one hand, while infection spreading is controlled by the synthesis of specific proteins like type-I interferons (IFNs) and pro-inflammatory cytokines on the other hand. How do these two apparent conflicting responses cooperate within the same infected cells to mount effective defenses against pathogens? What are the molecules or the complexes resolving this contradiction over time? Some recent studies reveal unanticipated connections between innate immunity and stress pathways, giving important clues on how the cellular responses are orchestrated to limit infection efficiently. Copyright © 2015. Published by Elsevier B.V.FEBS letters 05/2015; 11. DOI:10.1016/j.febslet.2015.05.006 · 3.34 Impact Factor
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ABSTRACT: Global fish production from aquaculture has rapidly grown over the past decades, and grass carp shares the largest portion. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in tremendous loss of grass carp (Ctenopharyngodon idella) industry. During the past years, development of molecular biology and cellular biology technologies has promoted significant advances in the understanding of the pathogen and the immune system. Immunoprophylaxis based on stimulation of the immune system of fish has also got some achievements. In this review, authors summarize the recent progresses in basic researches on GCRV; viral nucleic acid sensors, high-mobility group box proteins (HMGBs); pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and retinoic acid inducible gene I-(RIG-I-) like receptors (RLRs); antiviral immune responses induced by PRRs-mediated signaling cascades of type I interferon (IFN-I) and IFN-stimulated genes (ISGs) activation. The present review also notices the potential applications of molecule genetic markers. Additionally, authors discuss the current preventive and therapeutic strategies (vaccines, RNAi, and prevention medicine) and highlight the importance of innate immunity in long term control for grass carp hemorrhagic disease.Journal of Immunology Research 02/2015; 2015:Article ID 670437. DOI:10.1155/2015/670437 · 2.93 Impact Factor
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ABSTRACT: The prototypic response to viral infection involves the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), leading to the activation of transcription factors such as IRF3 and NFkB and production of type 1 IFN. While this response can lead to the induction of hundreds of IFN-stimulated genes (ISGs) and recruitment and activation of immune cells, such a comprehensive response is likely inappropriate for routine low level virus exposure. Moreover, viruses have evolved a plethora of immune evasion strategies to subvert antiviral signalling. There is emerging evidence that cells have developed very sensitive methods of detecting not only specific viral PAMPS, but also more general danger or stress signals associated with viral entry and replication. Such stress-induced cellular responses likely serve to prime cells to respond to further PAMP stimulation or allow for a rapid and localized intracellular response independent of IFN production and its potential immune sequelae. This review discusses diversity in innate antiviral players and pathways, the role of “danger” sensing, and how alternative pathways, such as the IFN-independent pathway, may serve to prime cells for further pathogen attack.Cytokine & Growth Factor Reviews 10/2014; DOI:10.1016/j.cytogfr.2014.07.002 · 6.54 Impact Factor