Post-Translational Modifications of Coronavirus Proteins: Roles and Function

Fung, To Sing; Liu, Ding Xiang

doi:10.2217/fvl-2018-0008

Cited by 216 publications

(232 citation statements)

References 205 publications

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“…Very little information is available on the glycosylation of CoV E and its role. The IBV E protein has been suggested to contain a single glycosylation site in its luminal N-terminus, while SARS-CoV E has been predicted to contain two potential glycosylation sites [132]. Based on the topology of IBV E, Corse and Machamer [60] proposed that it could be glycosylated on asparagine residue five (N5) of the Nterminus.…”

Section: Glycosylationmentioning

confidence: 99%

Coronavirus envelope protein: current knowledge

Schoeman

Fielding

2019

Virol J

1,823

1,859

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Background Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. Main body This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. Conclusions The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.

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Section: Glycosylationmentioning

confidence: 99%

Coronavirus envelope protein: current knowledge

Schoeman

Fielding

2019

Virol J

1,823

1,859

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“…Coronavirus M proteins are invariably glycosylated in the luminal ectodomain. While the M protein of some lineage A Betacoronaviruses is O-linked glycosylated, those of other coronaviruses are exclusively Nlinked (Fung and Liu, 2018). Only a single N-glycosylation site has been identified in the SARS-CoV M protein at N4 (Hu et al, 2003;Voss et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Although IBV M protein is presumably post-translationally inserted into the ER membrane, N-linked glycosylation of its ectodomain is nonetheless dependent on modification enzymes inside the ER lumen (Fung and Liu, 2018). We have previously shown that IBV infection activates the PERK-eIF2α and IRE1-XBP1 branches of the UPR signaling pathway.…”

Section: Effect Of N3d/n6d Mutations On Ibv-induced Er Stress Responsmentioning

confidence: 99%

“…Whereas M protein of some lineage A Betacoronaviruses, such as mouse hepatitis virus (MHV), bovine coronavirus and human coronavirus-OC43 (HCoV-OC43), is modified by O-linked glycosylation, M protein of other coronaviruses have been shown to be exclusively N-linked glycosylated (Holmes et al, 1981;Lapps et al, 1987;Mounir and Talbot, 1992;Hogue and Nayak, 1990;Utiger et al, 1995;Stern and Sefton, 1982;Dea et al, 1990). Different functions have been assigned to the oligosaccharide side chains, including protein folding, structure stability, intracellular sorting, and the induction of immune response (Drickamer and Taylor, 1998;Helenius and Aebi, 2001;Fung and Liu, 2018).…”

Section: Introductionmentioning

confidence: 99%

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N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis

et al. 2019

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A B S T R A C TCoronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly. Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated. In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV). Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells. However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines. Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.

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“…18 There are significant post-translational modifications in the S protein. The spike protein ectodomain is heavily glycosylated with heterogeneous N-linked glycans 19 and exists in a prefusion and a postfusion conformation. The oligosaccharides could influence priming by host proteases and determine antibody recognition.…”

Section: (A Class I Viral Fusion Protein Is a Viral Protein Primed Bymentioning

confidence: 99%

Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein

2020

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The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called COVID-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be ‘preactivated’ and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.

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Post-Translational Modifications of Coronavirus Proteins: Roles and Function

Cited by 216 publications

References 205 publications

Coronavirus envelope protein: current knowledge

Coronavirus envelope protein: current knowledge

N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis

Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein

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