How Do Viruses Interact with Stress-Associated RNA Granules?

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
PLoS Pathogens (Impact Factor: 8.06). 06/2012; 8(6):e1002741. DOI: 10.1371/journal.ppat.1002741
Source: PubMed
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    • "SG formation may have evolved as an effective cell-autonomous strategy employed to fight viral infections, which rely on the translational machinery of infected cells for viral protein production; SG formation can thus block viral replication (Beckham and Parker, 2008). However, viruses including poliovirus have evolved counterstrategies: they actively block the host cell's ability to form SGs during the infection (Lloyd, 2012), allowing translation of viral RNAs to continue, and so thwarting an otherwise powerful defence mechanism that may form part of the innate immune system. The bacterium Shigella has been shown to cause SG formation in infected cells, albeit as a response to pathogen-induced amino acid starvation (Tattoli et al., 2012). "
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    ABSTRACT: Organisms have evolved numerous strategies to control infection by an array of intracellular pathogens. One cell autonomous pathogen control strategy is global inhibition of protein synthesis via stress granule (SG) formation. SGs are induced by stressful stimuli such as oxidative stress and nutrient deprivation, and are known to counteract both viral and bacterial infections. Pathogens, in turn, may actively block an infected cell's ability to form SGs. In vitro and in vivo, many liver stage malaria parasites are eliminated during development. We show here that SG formation is not amongst the strategies used for elimination of parasites from hepatocytes. Neither cell traversal, sporozoite invasion, nor rapid parasite growth leads to the formation of SGs. Furthermore, Plasmodium berghei infection does not compromise the ability of infected cells to assemble SGs in response to oxidative or nutritional stress. Plasmodium infection is therefore not detected by hepatocytes as a strong stressor necessitating global translational repression in response, highlighting the idea that Plasmodium has evolved strategies to ensure its remarkable growth in the hepatocyte while maintaining host cell homeostasis.
    Biology Open 12/2013; 3(1). DOI:10.1242/bio.20136833 · 2.42 Impact Factor
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    • "Host RNAs undergo extensive degradation and turnover, as do viral RNAs (Lloyd, 2012). The participation of RNA decay pathways in viral RNA recombination has been studied in TBSV by the Nagy group (Jiang et al., 2010; Jaag et al., 2011). "
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    ABSTRACT: RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA-RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (1) How various factors modulate the ability of viral replicase to switch templates, (2) What is the intracellular location of RNA-RNA template switchings, (3) Mechanisms and factors responsible for non-replicative RNA recombination, (4) Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.
    Frontiers in Plant Science 03/2013; 4:68. DOI:10.3389/fpls.2013.00068 · 3.95 Impact Factor
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    ABSTRACT: Dynamic, mRNA-containing stress granules (SGs) form in the cytoplasm of cells under environmental stresses including viral infection. Many viruses appear to employ mechanisms to disrupt the formation of SGs on their mRNAs, suggesting that they represent a cellular defence against infection. Here, we report that early in Semliki Forest virus infection, the C-terminal domain of the viral non-structural protein 3 (nsP3) forms a complex with Ras-GAP SH3-domain binding protein (G3BP) and sequesters it into viral RNA replication complexes in a manner that inhibits the formation of SGs on viral mRNAs. A viral mutant carrying a C-terminal truncation of nsP3 induces more persistent SGs and is attenuated for propagation in cell culture. Importantly, we also show that the efficient translation of viral mRNAs containing a translation enhancer sequence also contributes to the disassembly of SGs in infected cells. Further, we show that the nsP3/G3BP interaction also blocks SGs induced by other stresses than virus infection. This is one of few described viral mechanisms for SG disruption and underlines the role of SGs in anti-viral defence.
    Molecular biology of the cell 10/2012; 23(24). DOI:10.1091/mbc.E12-08-0619 · 5.98 Impact Factor
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