Who Regulates Whom? An Overview of RNA Granules and Viral Infections

Poblete-Durán, Natalia; Prades-Pérez, Yara; Vera-Otárola, Jorge; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando

doi:10.3390/v8070180

Cited by 82 publications

(111 citation statements)

References 271 publications

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“…To overcome host translation shutoff, several RNA viruses evolved different strategies, including mechanisms that interfere with SG formation (8, 9). It has been reported that DENV inhibits SG formation in baby hamster kidney (BHK-21) cells by sequestering the SG-initiating proteins T cell internal antigen-1 (TIA-1) and TIA-1-related protein R (TIAR) on the 3′ untranslated region (UTR) of its RNA genome (36), although we found previously that infection of Huh7 cells with DENV induced few sporadically oscillating SGs (56).…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of protein synthesis is tightly linked to the assembly of stress granules (SGs), which are cytosolic aggregates of stalled translation preinitiation complexes (5–7). As they require an intact translation machinery to translate their viral genome, several viruses antagonize SG formation during infection, although some may also exploit SG responses for their replication (8, 9). …”

Section: Introductionmentioning

confidence: 99%

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Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses

Roth

Magg

Uch

et al. 2017

mBio

122

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As obligate parasites, viruses strictly depend on host cell translation for the production of new progeny, yet infected cells also synthesize antiviral proteins to limit virus infection. Modulation of host cell translation therefore represents a frequent strategy by which viruses optimize their replication and spread. Here we sought to define how host cell translation is regulated during infection of human cells with dengue virus (DENV) and Zika virus (ZIKV), two positive-strand RNA flaviviruses. Polysome profiling and analysis of de novo protein synthesis revealed that flavivirus infection causes potent repression of host cell translation, while synthesis of viral proteins remains efficient. Selective repression of host cell translation was mediated by the DENV polyprotein at the level of translation initiation. In addition, DENV and ZIKV infection suppressed host cell stress responses such as the formation of stress granules and phosphorylation of the translation initiation factor eIF2α (α subunit of eukaryotic initiation factor 2). Mechanistic analyses revealed that translation repression was uncoupled from the disruption of stress granule formation and eIF2α signaling. Rather, DENV infection induced p38-Mnk1 signaling that resulted in the phosphorylation of the eukaryotic translation initiation factor eIF4E and was essential for the efficient production of virus particles. Together, these results identify the uncoupling of translation suppression from the cellular stress responses as a conserved strategy by which flaviviruses ensure efficient replication in human cells.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses

Roth

Magg

Uch

et al. 2017

mBio

122

View full text Add to dashboard Cite

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“…Viruses of many classes can modulate SG formation and impact virus infections (33,34). The mechanisms that underlie this process and the effects that it has on the host to facilitate infection are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein

Khong

Kerr

Yeung

et al. 2017

J Virol

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Stress granules (SGs) are cytosolic ribonucleoprotein aggregates that are induced during cellular stress. Several viruses modulate SG formation, suggesting that SGs have an impact on virus infection. However, the mechanisms and impact of modulating SG assembly in infected cells are not completely understood. In this study, we identify the dicistrovirus cricket paralysis virus 1A (CrPV-1A) protein that functions to inhibit SG assembly during infection. Moreover, besides inhibiting RNA interference, CrPV-1A also inhibits host transcription, which indirectly modulates SG assembly. Thus, CrPV-1A is a multifunctional protein. We identify a key R146A residue that is responsible for these effects, and mutant CrPV(R146A) virus infection is attenuated in Drosophila melanogaster S2 cells and adult fruit flies and results in increased SG formation. Treatment of CrPV(R146A)-infected cells with actinomycin D, which represses transcription, restores SG assembly suppression and viral yield. In summary, CrPV-1A modulates several cellular processes to generate a cellular environment that promotes viral translation and replication.IMPORTANCE RNA viruses encode a limited set of viral proteins to modulate an array of cellular processes in order to facilitate viral replication and inhibit antiviral defenses. In this study, we identified a viral protein, called CrPV-1A, within the dicistrovirus cricket paralysis virus that can inhibit host transcription, modulate viral translation, and block a cellular process called stress granule assembly. We also identified a specific amino acid within CrPV-1A that is important for these cellular processes and that mutant viruses containing mutations of CrPV-1A attenuate virus infection. We also demonstrate that the CrPV-1A protein can also modulate cellular processes in human cells, suggesting that the mode of action of CrPV-1A is conserved. We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellular environment in virus-infected cells that permits productive virus infection.

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“…Among these, the best‐characterized RNA granules in the cytosol of somatic cells are processing bodies (P‐bodies) and stress granules (SGs), both typically encompassing mRNPs not engaged in translation . Such RNA granules are emerging as key control elements of messenger RNA (mRNA) metabolism and their deregulation has been linked to various human pathogenic conditions including cancer, degenerative disorders and viral infections …”

Section: Introductionmentioning

confidence: 99%

Hepatitis C virus plays with fire and yet avoids getting burned. A review for clinicians on processing bodies and stress granules

Fernández-Carrillo

Pérez‐Vilaró

Díez

et al. 2017

Liver International

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Over the last few years, many reports have defined several types of RNA cell granules composed of proteins and messenger RNA (mRNA) that regulate gene expression on a post-transcriptional level. Processing bodies (P-bodies) and stress granules (SGs) are among the best-known RNA granules, only detectable when they accumulate into very dynamic cytosolic foci. Recently, a tight association has been found between positive-stranded RNA viruses, including hepatitis C virus (HCV), and these granules.The present article offers a comprehensive review on the complex and paradoxical relationship between HCV, P-bodies and SGs from a translational perspective. Despite the fact that components of P-bodies and SGs have assiduously controlled mRNA expression, either by sequestration or degradation, for thousands of years, HCV has learned how to dangerously exploit certain of them for its own benefit in an endless biological war. Thus, HCV has gained the ability to hack ancient host machineries inherited from prokaryotic times. While P-bodies and SGs are crucial to the HCV cycle, in the interferon-free era we still lack detailed knowledge of the mechanisms involved, processes that may underlie the long-term complications of HCV infection.

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Who Regulates Whom? An Overview of RNA Granules and Viral Infections

Cited by 82 publications

References 271 publications

Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses

Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses

Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein

Hepatitis C virus plays with fire and yet avoids getting burned. A review for clinicians on processing bodies and stress granules

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