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SARS-CoV-2 ORF8 Forms Intracellular Aggregates and Inhibits IFNγ-Induced Antiviral Gene Expression in Human Lung Epithelial Cells

Overview of attention for article published in Frontiers in immunology, June 2021
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • High Attention Score compared to outputs of the same age and source (89th percentile)

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1 blog
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13 X users

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46 Dimensions

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61 Mendeley
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Title
SARS-CoV-2 ORF8 Forms Intracellular Aggregates and Inhibits IFNγ-Induced Antiviral Gene Expression in Human Lung Epithelial Cells
Published in
Frontiers in immunology, June 2021
DOI 10.3389/fimmu.2021.679482
Pubmed ID
Authors

Hua Geng, Saravanan Subramanian, Longtao Wu, Heng-Fu Bu, Xiao Wang, Chao Du, Isabelle G. De Plaen, Xiao-Di Tan

Abstract

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a disease that involves significant lung tissue damage. How SARS-CoV-2 infection leads to lung injury remains elusive. The open reading frame 8 (ORF8) protein of SARS-CoV-2 (ORF8SARS-CoV-2) is a unique accessory protein, yet little is known about its cellular function. We examined the cellular distribution of ORF8SARS-CoV-2 and its role in the regulation of human lung epithelial cell proliferation and antiviral immunity. Using live imaging and immunofluorescent staining analyses, we found that ectopically expressed ORF8SARS-CoV-2 forms aggregates in the cytosol and nuclear compartments of lung epithelial cells. Using in silico bioinformatic analysis, we found that ORF8SARS-CoV-2 possesses an intrinsic aggregation characteristic at its N-terminal residues 1-18. Cell culture did not reveal any effects of ORF8SARS-CoV-2 expression on lung epithelial cell proliferation and cell cycle progression, suggesting that ORF8SARS-CoV-2 aggregates do not affect these cellular processes. Interestingly, ectopic expression of ORF8SARS-CoV-2 in lung epithelial cells suppressed basal expression of several antiviral molecules, including DHX58, ZBP1, MX1, and MX2. In addition, expression of ORF8SARS-CoV-2 attenuated the induction of antiviral molecules by IFNγ but not by IFNβ in lung epithelial cells. Taken together, ORF8SARS-CoV-2 is a unique viral accessory protein that forms aggregates when expressing in lung epithelial cells. It potently inhibits the expression of lung cellular anti-viral proteins at baseline and in response to IFNγ in lung epithelial cells, which may facilitate SARS-CoV-2 escape from the host antiviral innate immune response during early viral infection. In addition, it seems that formation of ORF8SARS-CoV-2 aggregate is independent from the viral infection. Thus, it would be interesting to examine whether any COVID-19 patients exhibit persistent ORF8 SARS-CoV-2 expression after recovering from SARS-CoV-2 infection. If so, the pathogenic effect of prolonged ORF8SARS-CoV-2 expression and its association with post-COVID symptoms warrant investigation in the future.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 61 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 11%
Student > Master 6 10%
Student > Doctoral Student 5 8%
Student > Ph. D. Student 5 8%
Student > Bachelor 4 7%
Other 4 7%
Unknown 30 49%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 18%
Medicine and Dentistry 8 13%
Immunology and Microbiology 4 7%
Agricultural and Biological Sciences 3 5%
Psychology 2 3%
Other 4 7%
Unknown 29 48%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 November 2023.
All research outputs
#2,771,799
of 25,864,668 outputs
Outputs from Frontiers in immunology
#2,847
of 32,510 outputs
Outputs of similar age
#67,348
of 461,832 outputs
Outputs of similar age from Frontiers in immunology
#154
of 1,455 outputs
Altmetric has tracked 25,864,668 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 32,510 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done particularly well, scoring higher than 91% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 461,832 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 1,455 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 89% of its contemporaries.