Rnase l virus

Zika virus pathogenesis and tissue tropism. Cell Host Microbe 21 — Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med — Evolution of two major Zika virus lineages: implications for pathology, immune response, and vaccine development. Front Immunol 9 Regulation of flavivirus RNA synthesis and replication. Curr Opin Virol 9 — Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5 — Ultrastructural characterization of Zika virus replication factories.

Cell Rep 18 — Rewiring cellular networks by members of the Flaviviridae family. Nat Rev Microbiol 16 — Paul D, Bartenschlager R. Architecture and biogenesis of plus-strand RNA virus replication factories. World J Virol 2 — Best SM. The many faces of the flavivirus NS5 protein in antagonism of type I interferon signaling. J Virol 91 :e Antagonism of type I interferon by flaviviruses.

Biochem Biophys Res Commun — Cell Host Microbe 19 — Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro.

Cell Discov 3 Zika virus antagonizes type I interferon responses during infection of human dendritic cells. PLoS Pathog 13 :e Zika virus inhibits type-I interferon production and downstream signaling. EMBO Rep 17 — J Immunol — RNase L plays a role in the antiviral response to West Nile virus.

J Virol 80 — Dong B, Silverman RH. J Biol Chem — Cell Host Microbe 17 — Elife 6 :e EMBO J 16 — A study of the interferon antiviral mechanism: apoptosis activation by the A system. J Exp Med — Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe 11 — Li Y, Weiss SR. Antagonism of RNase L is required for murine coronavirus replication in Kupffer cells and liver sinusoidal endothelial cells but not in hepatocytes.

J Virol 90 — Cell-type-specific effects of RNase L on viral induction of beta interferon. These studies were supported by grants from the NIH to R. You can also search for this author in PubMed Google Scholar.

Correspondence to Robert H. Reprints and permissions information is available at www. The authors declare no competing financial interests. Reprints and Permissions.

Download citation. Received : 29 May Accepted : 21 June Published : 25 July Issue Date : 16 August Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Advanced search. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. Abstract Antiviral innate immunity is initiated in response to RNA molecules that are produced in virus-infected cells 1.

Access through your institution. Buy or subscribe. This is a preview of subscription content. Change institution. Buy article Get time limited or full article access on ReadCube. References 1 Saito, T. Acknowledgements We thank M. Washington: American Society for Microbiology; The predominant virus antigen burden is present in macrophages in Theiler's murine encephalomyelitis virus-induced demyelinating disease. Journal of virology. Theiler's virus infection: a model for multiple sclerosis.

Clinical microbiology reviews. The genetics of the persistent infection and demyelinating disease caused by Theiler's virus. Annual review of microbiology. Polyprotein processing of Theiler's murine encephalomyelitis virus. A protein critical for a Theiler's virus-induced immune system-mediated demyelinating disease has a cell type-specific antiapoptotic effect and a key role in virus persistence.

Theiler's virus L protein is targeted to the mitochondrial outer membrane. PLoS pathogens. International journal of molecular sciences. New advances in our understanding of the "unique" RNase L in host pathogen interaction and immune signaling.

Synthesis of low molecular weight inhibitor of protein synthesis with enzyme from interferon-treated cells. The Journal of biological chemistry. Dong B, Silverman RH. Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L.

The EMBO journal. A study of the interferon antiviral mechanism: apoptosis activation by the A system. Siddiqui MA, Malathi K. RNase L triggers autophagy in response to viral infections.

A bipartite model of A-dependent RNase L. Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L.

Innate immune messenger A tethers human RNase L into active high-order complexes. Cell reports. Dimeric structure of pseudokinase RNase L bound to A reveals a basis for interferon-induced antiviral activity. Molecular cell. PKR and RNase L contribute to protection against lethal West Nile Virus infection by controlling early viral spread in the periphery and replication in neurons. RNase L and double-stranded RNA-dependent protein kinase exert complementary roles in islet cell defense during coxsackievirus infection.

Journal of immunology. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology.

Silverman RH. Viral encounters with 2',5'-oligoadenylate synthetase and RNase L during the interferon antiviral response. Drappier M, Michiels T. Current opinion in virology. Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. A phylogenetically conserved RNA structure in the poliovirus open reading frame inhibits the antiviral endoribonuclease RNase L.

Alternative function of a protein kinase homology domain in 2', 5'-oligoadenylate dependent RNase L. Nucleic acids research. Small-molecule activators of RNase L with broad-spectrum antiviral activity. Susceptibility of inbred mice to chronic central nervous system infection by Theiler's murine encephalomyelitis virus. Infection and immunity. An early, abundant cytotoxic T-lymphocyte response against Theiler's virus is critical for preventing viral persistence.

Fusion-defective mutants of mouse hepatitis virus A59 contain a mutation in the spike protein cleavage signal.

Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Expression cloning of A-dependent RNAase: a uniquely regulated mediator of interferon action. Simian virus infected, interferon-treated cells contain 2',5'-oligoadenylates which do not activate cleavage of RNA.

Autophagy promotes the replication of encephalomyocarditis virus in host cells. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences.

S6, A to C. RNase L—mediated inhibition of mRNA export would also be expected to limit translation of transcriptionally induced antiviral mRNAs, which could be detrimental to the antiviral response. However, since this response was heterogeneous with respect to individual cells Figs. Such a function would be important for ensuring cytokine production while potentially preventing the overproduction of cytokines, which can cause cytokine storm phenomena. Three primary observations support these hypotheses.

S7 , consistent with a previous study Markers represent the mean SD from at least six replicates. The number and percentage of smFISH foci localized to the nucleus are shown in the top right corners. Nuclei were determined by DAPI staining not shown for space and clarity and are outlined. Additional images are shown in figs. S8 and S9. Each dot represents a Ct value from an individual experiment.

The graph below shows the mean percentage and SD of apoptotic cells. We present several observations documenting new aspects of the innate immune response. Similar to host antiviral mRNAs 9 , 10 , the high transcriptional rates of viral mRNAs and their structure, as well as their localization to replication factories and association with viral proteins 8 , likely contribute to their ability to escape the effects of RNase L—mediated mRNA decay.

We also identified a new mechanism by which RNase L reduces host and viral gene expression, whereby RNase L activation inhibits mRNA export of host and viral mRNAs, which reduces their translation by preventing their association with ribosomes in the cytoplasm. This is based on the observations that host and viral mRNAs accumulate in the nucleus of cells that have activated RNase L, and this correlates to reduced protein expression from these transcripts Figs.

One function of RNase L—mediated inhibition of mRNA export is to limit viral protein production by limiting gene expression from viruses that replicate in the nucleus. Our data suggest that this is a primary mechanism by which RNase L limits influenza protein production since nuclear accumulation of influenza mRNAs is required for a reduction in their translation in cells with activated RNase L Fig. We suggest that the heterogeneous and temporal nature between individual cells allows for sufficient production of cytokines to limit viral replication Figs.

S7 to S9 S7 to S9. This would promote localized epithelial cell—specific antiviral signaling before systemic type I IFN signaling Combined, these functions may prevent systematic overproduction of cytokines, which can lead to cytokine storm, sepsis, and autoimmune disorders in response to viral infection 31 — The A cell line was provided by C.

Sullivan The University of Texas at Austin. Cells were fixed 48 hours after infection. Cells were fixed 7 hours after infection.

Immunoblot analysis was performed as described in 9. After three washes, cells were fixed, and then smFISH protocol was performed. Between 10 and 15 Z planes at 0. Z planes were stacked, and minimum and maximum display values were set in ImageJ for each channel to properly view fluorescence. Fluorescence intensity was measured in ImageJ. Single cells were outlined by determining the cell boundaries via background fluorescence and mean intensity, and integrated intensity was measured in the relevant channels.

Single cells were isolated for analysis by defining their borders via background fluorescence.