Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane

By M. Frieman, B. Yount, M. Heise, Sarah A. Kopecky-Bromberg, P. Palese, Ralph S. Baric. 2007

522 citations recorded by the source corpus.

Subfields: Animal Science and Zoology, Immunology, Infectious Diseases

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

In Immunology

In Infectious Diseases

Citations in the corpus

SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through Interactions with Rae1 and Nup98 (2021, background): “Both SARS-CoV and SARS-CoV-2 have been demonstrated to block nuclear import of the transcription factor, STAT1, during infection in cell culture (3, 14).”
Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor (2021, unknown): “Although the N-terminus alpha-helix has been conserved, SARS-CoV-2 and SARS-CoV Orf6 only show about 67% overall similarity in codon sequence [12].”
SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling (2020, methodology): “For instance, the nonstructural protein Nsp1 of SARS-CoV was shown to decrease phosphorylation levels of STAT1 (22); the accessory proteins Orf3b and Orf6 appeared to inhibit IFN production and signaling by blocking nuclear translocation of transcription factors (20, 21); and the SARS-CoV-2 encoded ”
Coronavirus Pathogenesis (2011, background): “The C-terminal tail of orf6 binds karyopherin alpha (KPNA)2, which recruits KPNB1 a component of the classical nuclear import complex, thus blocking proteins with classical import signals (Frieman et al., 2007; Hussain et al., 2008).”
Sarbecovirus ORF6 proteins hamper induction of interferon signaling (2021, unknown): “ORF6 proteins of SARS-CoV-2 lineages inhibit activation of IFN signaling more potently than those of SARS-CoV lineages Because previous reports have suggested that SARS-CoVORF6 has the ability to inhibit IFN-I activation as well as upregulation of IFN-stimulated genes (ISGs) (Frieman et al., 2007; K”
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro (2020, background): “In addition, the SARS-CoV accessory protein ORF6 has been shown to antagonize the antiviral activity of the STAT1 transcription factor by sequestering IMPα/β1 on the rough ER/Golgi membrane (Frieman et al., 2007) .”
Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans (2012, background): “, by interfering with cellular innate immune signaling (43).”
Accessory proteins of SARS-CoV and other coronaviruses (2014, background): “Notably, some coronaviral accessory proteins have also been shown to modulate the interferon signaling, which is of paramount importance for host antiviral immunity (Frieman et al., 2007; Dedeurwaerder et al., 2014; Zhang et al., 2013; Cruz et al., 2013).”
Evasion of Type I Interferon by SARS-CoV-2 (2020, result): “Our SARS-CoV-2 ORF6 results are consistent with those of previous studies showing that SARSCoV ORF6 inhibits both IFN production and STAT1 signaling by interacting with KPNA2 and altering nuclear import (Frieman et al., 2007; Kopecky-Bromberg et al., 2007).”
The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis (2012, background): “ORF6 is a type I IFN antagonist, and its expression suppresses the induction of both IFN as well as the IFN signaling pathways [68,94].”
Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1–Nup98 Complex to Compete With mRNA Nuclear Export (2022, background): “SARS-CoV-1 Orf6 has been reported to interfere with interferon signaling by preventing nucleocytoplasmic transport (Frieman et al., 2007).”