Giuseppe MichieliApr 13, 2024

Positive #selection underlies repeated knockout of #ORF8 in #SARS-CoV-2 #evolution https://www.nature.com/articles/s41467-024-47599-5

SARS-CoV-2 constantly evolves but the roles of resulting #mutations are not always clear. In this study, the authors report that ORF8 knockout confers a #fitness advantage to SARS-CoV-2 using genomic #surveillance data, highlighting how different types of adaptations across the SARS-CoV-2 genome can drive variant fitness.

Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution - Nature Communications

SARS-CoV-2 constantly evolves but the roles of resulting mutations are not always clear. In this study, the authors report that ORF8 knockout confers a fitness advantage to SARS-CoV-2 using genomic surveillance data, highlighting how different types of adaptations across the SARS-CoV-2 genome can drive variant fitness.

Nature
Giuseppe MichieliFeb 8, 2024

#Virological characteristics of the #SARS-CoV-2 #Omicron #XBB15 #variant, Nat Commun.: https://www.nature.com/articles/s41467-024-45274-3

-- We provide intrinsic pathogenicity of XBB.1 & XBB.1.5 in hamsters. ...we find that #ORF8 nonsense mutation of XBB.1.5 resulted in impairment of #MHC suppression. In vivo experiments using recombinant viruses reveal that XBB.1.5 mutations are involved with reduced virulence of XBB.1.5... our study identifies 2 viral functions defined difference between XBB.1 & XBB.1.5.

Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant - Nature Communications

XBB.1.5 of SARS-CoV-2 is a descendant of XBB.1 and has mutations in spike and ORF8, making it more infectious to humans. Here, the authors examined in detail the differences in virological properties of the two variants.

Nature
Matt WillemsenMay 12, 2023
The Latest COVID Variants Have a Surprising Feature in Common
Over and over again, genetic mutations are preventing a protein once thought to be key to the virus’s success from being expressed.
spike gets all the glory and infamy; it is the protein targeted by vaccines, and it is the protein that keeps shape-shifting in new variants. But lately, something strange has been happening with another protein called ORF8, once thought to be a crucial player. The virus keeps losing ORF8—over and over again
https://www.theatlantic.com/science/archive/2023/05/coronavirus-evolution-orf8-protein-gene-loss/674017/ #covidｰ19 #variants #ORF8 #spike
The Latest COVID Variants Have a Surprising Thing in Common

Over and over again, genetic mutations are preventing a protein once thought to be key to the virus’s success from being expressed.

The Atlantic
Raj Rajnarayanan Apr 26, 2023

#SARSCoV2 is missing a piece and it doesn't even care

A quick tweetorial from @PeacockFlu

H/T @siamosolocani @LongDesertTrain
#ORF8 #AccessoryProtein #COVID19

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RT @PeacockFlu
Inspired by some recent discussion we wrote a short report for virological about how one of SARS-CoV-2's accessory proteins (called ORF8) appears to have gone missing over the last year (with @LongDesertTrain and @siamosolocani) https://twitter.com/virologic…
https://twitter.com/PeacockFlu/status/1651209027366313984

Raj Rajnarayanan Apr 26, 2023

#SARSCoV2 is missing a piece and it doesn't even care

Tweetsplainer from @PeacockFlu

H/T @siamosolocani @LongDesertTrain

#ORF8 #AccessoryProtein #COVID19
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RT @PeacockFlu
Inspired by some recent discussion we wrote a short report for virological about how one of SARS-CoV-2's accessory proteins (called ORF8) appears to have gone missing over the last year (with @LongDesertTrain and @siamosolocani) https://twitter.com/virological_o…
https://twitter.com/PeacockFlu/status/1651209027366313984

Giuseppe MichieliJan 23, 2023
Unconventional #secretion of unglycosylated #ORF8 is critical for the #cytokine #storm during #SARS-CoV-2 infection https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011128
Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

Author summary Cytokine storm is an important point in the transition of COVID-19 from mild to severe/critical diseases. Clinical cases show that the viral loads in patients are not directly proportional to the severity of disease symptoms, which indicates that in addition to virion release, there is a unique indirect cellular communication mechanism in the development of cytokine storm. In this study, we found that accessory protein ORF8 is a secretory protein that acts as messenger for the inter-cellular communication between alveolar epithelial cells (the main targets of virus) and monocytes/macrophages (the main executors of cytokine storm). Our findings are helpful to understand the occurrence of cytokine storm caused by SARS-CoV-2, and provide a potential strategy for COVID-19 therapeutic drugs.