Coronavirus Spike Protein Inhibits Host Cell Translation by Interaction with eIF3f

Xiao, Han; Xu, Ling; Yamada, Yoshiyuki; Liu, Ding Xiang

doi:10.1371/journal.pone.0001494

Cited by 74 publications

(74 citation statements)

References 38 publications

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“…However, eIF3-f is essential for Schizosaccharomyces pombe viability, and its depletion markedly decreases the global protein synthesis in fission yeast (11). The same effect on protein translation was recently described in cells infected with the coronaviruses severe acute respiratory syndrome coronavirus (SARS coV) and coronavirus infectious bronchitis virus (12). In humans, down-regulation of eIF3-f is associated with several tumors (13,14), and when overexpressed, eIF3-f negatively regulates cell growth by affecting translation efficiency and activation of apoptosis (15).…”

mentioning

confidence: 55%

MAFbx/Atrogin-1 Controls the Activity of the Initiation Factor eIF3-f in Skeletal Muscle Atrophy by Targeting Multiple C-terminal Lysines

Csibi

Leibovitch²,

Cornille³

et al. 2009

Journal of Biological Chemistry

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We recently presented evidence that the subunit eIF3-f of the eukaryotic initiation translation factor eIF3 that interacts with the E3-ligase Atrogin-1/muscle atrophy F-box (MAFbx) for polyubiquitination and proteasome-mediated degradation is a key target that accounts for MAFbx function during muscle atrophy. To understand this process, deletion analysis was used to identify the region of eIF3-f that is required for its proteolysis. Here, we report that the highly conserved C-terminal domain of eIF3-f is implicated for MAFbx-directed polyubiquitination and proteasomal degradation. Site-directed mutagenesis of eIF3-f revealed that the six lysine residues within this domain are required for full polyubiquitination and degradation by the proteasome. In addition, mutation of these six lysines (mutant K 5-10 R) displayed hypertrophic activity in cellulo and in vivo and was able to protect against starvation-induced muscle atrophy. Taken together, our data demonstrate that the C-terminal modifications, believed to be critical for proper eIF3-f regulation, are essential and contribute to a fine-tuning mechanism that plays an important role for eIF3-f function in skeletal muscle.Skeletal muscle is a dynamic tissue that has the capacity to continuously regulate its size in response to a variety of external cues including mechanical load, neural activity, hormones/ growth factors, stress, and nutritional status. In addition, skeletal muscle serves as the most significant repository for protein in the body, a source that is tapped to provide a pool of amino acids for tissue repair and gluconeogenesis under conditions of starvation and other stresses. The maintenance of muscle mass is controlled by a fine balance between catabolic and anabolic processes, which determine the level of muscle proteins and the diameter of muscle fibers. Muscle loss occurs as the result of a number of disparate conditions including cancer, diabetes, AIDS, sepsis, renal failure, aging, cachexia, and other systemic diseases (1). These diverse conditions result in reduced protein synthesis and increased protein breakdown. The process of atrophy is characterized by the activation of the ATP-dependent ubiquitin-proteasome proteolysis pathway (2). Proteins destined for degradation by the ubiquitin-proteasome pathway are marked by covalent linkage with a chain of ubiquitin molecules (Ub) 3 on lysine residue(s) for further degradation into short peptides by the 26 S proteasome. This process requires an Ub-activating enzyme (E1), an Ub-conjugating enzyme (E2), and an Ub ligase (E3) that acts as the last step of the cascade (3). E3 proteins regulate the timing and the substrate specificity in protein degradation. In multiple models of skeletal muscle atrophy, the muscle-specific F-box protein MAFbx/Atrogin-1 (MAFbx) is up-regulated and appears to be essential for accelerated muscle protein loss (4 -6). MAFbx mRNA increases 8 -40-fold in all types of atrophy studied, and this increase precedes the onset of muscle weight loss. Moreover, knock-out animals l...

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mentioning

confidence: 55%

MAFbx/Atrogin-1 Controls the Activity of the Initiation Factor eIF3-f in Skeletal Muscle Atrophy by Targeting Multiple C-terminal Lysines

Csibi

Leibovitch²,

Cornille³

et al. 2009

Journal of Biological Chemistry

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“…Antibodies against Myc and FLAG were from Sigma, and antibodies against actin were from Santa Cruz (Santa Cruz, CA). Polyclonal antibodies against IBV N and S proteins were raised in rabbits (40,41). Mouse antibodies against HA for indirect immunofluorescence assays was from ETC (Singapore).…”

Section: Methodsmentioning

confidence: 99%

Coronavirus Infection Induces DNA Replication Stress Partly through Interaction of Its Nonstructural Protein 13 with the p125 Subunit of DNA Polymerase δ

Huang

Fang

et al. 2011

Journal of Biological Chemistry

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Perturbation of cell cycle regulation is a characteristic feature of infection by many DNA and RNA viruses, including Coronavirus infectious bronchitis virus (IBV). IBV infection was shown to induce cell cycle arrest at both S and G 2 /M phases for the enhancement of viral replication and progeny production. However, the underlying mechanisms are not well explored. In this study we show that activation of cellular DNA damage response is one of the mechanisms exploited by Coronavirus to induce cell cycle arrest. An ATR-dependent cellular DNA damage response was shown to be activated by IBV infection. Suppression of the ATR kinase activity by chemical inhibitors and siRNA-mediated knockdown of ATR reduced the IBV-induced ATR signaling and inhibited the replication of IBV. Furthermore, yeast two-hybrid screens and subsequent biochemical and functional studies demonstrated that interaction between Coronavirus nsp13 and DNA polymerase ␦ induced DNA replication stress in IBV-infected cells. These findings indicate that the ATR signaling activated by IBV replication contributes to the IBV-induced S-phase arrest and is required for efficient IBV replication and progeny production.DNA damage response is a signal transduction pathway that coordinates cell cycle transition, DNA replication, and repair in response to DNA damage or replication stress (1, 2). It is essential for maintenance of genome integrity and cell survival. DNA damage response is primarily mediated by two related protein kinases, the ataxia-telangiectasia mutated (ATM) 2 and ATM/ Rad3-related (ATR). ATM is activated as a result of doublestranded breaks (DSBs) and is recruited to DSBs by Mre11-Rad50-NBS1 complex (3, 4). ATR, on the other hand, is activated by a wide range of DNA damage, including stalled DNA replication forks and the subsequent single-stranded lesion (ssDNA), base adducts, ultraviolet (UV)-induced nucleotide damage, and double-stranded breaks during S phase (1, 5). ATR is recruited to replication factor A (RPA)-coated ssDNA by ATR-interacting protein (ATRIP) (6, 7). When ATM or ATR is recruited to sites of damage, they phosphorylate and activate different substrates, including checkpoint kinase-2 (CHK2) and CHK1, respectively (1,8,9). A large number of overlapping substrates of ATM and ATR that might be involved in DNA damage response has been presented (e.g. H2AX, RPA32, p53, BRCA1) (10, 11). Those signaling modules finally lead to cell cycle arrest to allow for DNA repair or apoptosis in cases of severe DNA damage. In contrast to ATM, ATR prevents replication fork collapse at stalled replication forks and is essential for cell viability (7,(12)(13)(14)(15)(16)(17)(18).Many DNA viruses and retroviruses, including Epstein-Barr virus, herpes simplex virus 1, human Papillomavirus 16, human immunodeficiency virus (HIV), adenovirus, simian virus 40 (SV40), and Polyomavirus, are known to eliminate, circumvent, or exploit various aspects of cellular DNA damage response machinery to maximize their own replication. In RNA virus families, however,...

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“…In addition, the spike (S) protein of SARS-CoV and infectious bronchitis virus (IBV) can interact with eIF3f to inhibit host translation. This mechanism has been exploited by coronaviruses to counteract the host-antiviral response and to modulate coronavirus pathogenesis (Xiao et al, 2008). Wataru Kamitani had reported that the nsp1 protein of SARS-Cov utilizes a twopronged strategy to inhibit translation of host proteins: nsp1 blocked the formation of 80S by binding to the 40S ribosomal subunit and facilitated the degradation of the 5′-end of mRNA degradation, rendering the mRNA translationally inactive (Kamitani et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the rabies virus (RV) M protein can inhibit eukaryotic translation via a protein interaction with eIF3 h (Komarova et al, 2007). Furthermore, eIF3f can also interact with the S protein of SARS-CoV and infectious bronchitis virus (IBV) to inhibit expression of host genes (Xiao et al, 2008). In addition to inhibiting host translation, eIF3f can inhibit HIV replication by specifically impeding the 3′ end processing of HIV-1 mRNAs (Valente et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

EIF3i affects vesicular stomatitis virus growth by interacting with matrix protein

Pan

Song

et al. 2017

Veterinary Microbiology

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The matrix protein of vesicular stomatitis virus (VSV) performs multiple functions during viral genome replication and virion production and is involved in modulating multiple host signaling pathways that favor virus replication. To perform numerous functions within infected cells, the M protein needs to recruit cellular partners. To better understand the role of M during VSV replication, we looked for interacting partners by using the two-hybrid system. The eukaryotic translation initiation factor 3, subunit i (eIF3i) was identified to be an M-binding partner, and this interaction was validated by GST pull-down and laser confocal assays. Through a mutagenesis analysis, we found that some mutants of M between amino acids 122 and 181 impaired but did not completely abolish the M-eIF3i interaction. Furthermore, the knockdown of eIF3i by RNA interference decreased viral replication and transcription in the early stages but led to increase in later stages. VSV transcription was increased at 4h post-infection but was not changed at 8 and 12h post-infection after the over-expression of eIF3i. Finally, we also demonstrated that VSV could inhibit the activity of Akt1 and that the knockdown of eIF3i inhibited the expression of the ISGs regulated by phospho-Akt1. These results indicated that eIF3i may affect VSV growth by regulating the host antiviral response in HeLa cells.

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Coronavirus Spike Protein Inhibits Host Cell Translation by Interaction with eIF3f

Cited by 74 publications

References 38 publications

MAFbx/Atrogin-1 Controls the Activity of the Initiation Factor eIF3-f in Skeletal Muscle Atrophy by Targeting Multiple C-terminal Lysines

MAFbx/Atrogin-1 Controls the Activity of the Initiation Factor eIF3-f in Skeletal Muscle Atrophy by Targeting Multiple C-terminal Lysines

Coronavirus Infection Induces DNA Replication Stress Partly through Interaction of Its Nonstructural Protein 13 with the p125 Subunit of DNA Polymerase δ

EIF3i affects vesicular stomatitis virus growth by interacting with matrix protein

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