SARS-CoV-2 ORF8 reshapes the ER through forming mixed disulfides with ER oxidoreductases

Liu, Ping; Wang, Xi; Sun, Yiwei; Zhao, Hongyu; Cheng, Fang; Wang, Jifeng; Yang, Fuchao; Hu, Junjie; Zhao, Hong; Wang, Chih-chen; Wang, Lei

doi:10.1016/j.redox.2022.102388

Cited by 28 publications

(39 citation statements)

References 47 publications

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“…A secretory status, however, raises the intriguing question of how SARS-CoV-2 ORF8 can suppress the cell-surface expression of MHC I (15, 16), and has an interactome that includes predominantly host proteins associated with the ER quality control system (43,(54)(55)(56). These characteristics are more consistent with ORF8 accumulating in the ER, and there is mounting experimental evidence consistent with this (15,16,25). This in itself is also puzzling given that ORF8 does not harbor an apparent motif for ER retention.…”

Section: Structure-function Relationshipmentioning

confidence: 99%

“…It is also intriguing that multiple distinct host binding partners and functions have been attributed experimentally to SARS-CoV-2 ORF8 (11,12,15,16,(22)(23)(24)(25). Interactome studies of ORF8 have also mapped a broad interaction landscape that includes host proteins associated with ER stress and secretory pathways, complement and coagulation cascade, and INF-b signaling pathway (43,(54)(55)(56).…”

Section: Structure-function Relationshipmentioning

confidence: 99%

“…Viruses have evolved different strategies to utilize the UPR for viral replication. Interestingly, ORF8 alone can induce ER stress and a molecular mechanism has been proposed ( 22 , 25 ). It was suggested that ORF8 mimics an unfolded or folding intermediates thereby creating an imbalance in the protein folding milieu of the ER that leads to UPR activation.…”

Section: Modulation Of Host Immune Functionsmentioning

confidence: 99%

“…It was suggested that ORF8 mimics an unfolded or folding intermediates thereby creating an imbalance in the protein folding milieu of the ER that leads to UPR activation. Under ER stress, it was shown that ORF8 escapes protein degradation by forming mixed disulfide complexes with ER-resident oxidoreductases such as ERp44 and protein disulfide isomerase (PDI) ( 25 ). Although ERp57 was not specifically examined in this study, it is a prominent oxidoreductase in the ER ( 38 ) and it plays a critical role in MHC I folding and maturation ( 39 , 40 ).…”

Section: Modulation Of Host Immune Functionsmentioning

confidence: 99%

“…The results showed that ORF8 exhibits multiple functions directed mainly against host immune responses and affecting different biological pathways. Specifically, it was shown that ORF8 downregulates MHC I ( 15 , 16 ), antagonizes the IFN signaling pathway ( 11 , 12 ), interacts with transforming growth factor-beta 2 ( 22 ), activates interleukin 17 (IL-17) signaling pathway ( 23 , 24 ), and induces endoplasmic reticulum (ER) stress ( 22 , 25 ). The structure of SARS-CoV-2 ORF8 revealed an immunoglobulin (Ig)-like protein with unique characteristics, including the ability to homodimerize ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 ORF8: One protein, seemingly one structure, and many functions

Vinjamuri

Bouvier

2022

Front. Immunol.

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SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 encodes nine accessory proteins that are involved in host-pathogen interaction. ORF8 is unique among these accessory proteins. SARS-CoV-2 ORF8 shares a surprisingly low amino acid sequence similarity with SARS-COV ORF8 (30%), and it is presumed to have originated from bat. Studies have shown that ORF8 exerts multiple different functions that interfere with host immune responses, including the downregulation of MHC class I molecules. These functions may represent strategies of host immune evasion. The x-ray crystal structure of ORF8 revealed an immunoglobulin-like domain with several distinguishing features. To date, there are numerous unanswered questions about SARS-CoV-2 ORF8 protein and its structure-function relationship that we discuss in this mini-review. A better understanding of how ORF8 interacts with components of the immune system is needed for elucidating COVID-19 pathogenesis and to develop new avenues for the treatment of the disease.

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Section: Structure-function Relationshipmentioning

confidence: 99%

Section: Structure-function Relationshipmentioning

confidence: 99%

Section: Modulation Of Host Immune Functionsmentioning

confidence: 99%

Section: Modulation Of Host Immune Functionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 ORF8: One protein, seemingly one structure, and many functions

Vinjamuri

Bouvier

2022

Front. Immunol.

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Loss to gain: pseudogenes in microorganisms, focusing on eubacteria, and their biological significance

Yang,

Wang,

Qaidi

et al. 2024

Appl Microbiol Biotechnol

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Pseudogenes are defined as “non-functional” copies of corresponding parent genes. The cognition of pseudogenes continues to be refreshed through accumulating and updating research findings. Previous studies have predominantly focused on mammals, but pseudogenes have received relatively less attention in the field of microbiology. Given the increasing recognition on the importance of pseudogenes, in this review, we focus on several aspects of microorganism pseudogenes, including their classification and characteristics, their generation and fate, their identification, their abundance and distribution, their impact on virulence, their ability to recombine with functional genes, the extent to which some pseudogenes are transcribed and translated, and the relationship between pseudogenes and viruses. By summarizing and organizing the latest research progress, this review will provide a comprehensive perspective and improved understanding on pseudogenes in microorganisms. Key points • Concept, classification and characteristics, identification and databases, content, and distribution of microbial pseudogenes are presented. • How pseudogenization contribute to pathogen virulence is highlighted. • Pseudogenes with potential functions in microorganisms are discussed.

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SARS-CoV-2 ORF8 reshapes the ER through forming mixed disulfides with ER oxidoreductases

Cited by 28 publications

References 47 publications

SARS-CoV-2 ORF8: One protein, seemingly one structure, and many functions

SARS-CoV-2 ORF8: One protein, seemingly one structure, and many functions

Loss to gain: pseudogenes in microorganisms, focusing on eubacteria, and their biological significance

Deciphering ER stress-unfolded protein response relationship by visualizing unfolded proteins in the ER

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