Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists

By Sarah A. Kopecky-Bromberg, L. Martínez-Sobrido, M. Frieman, Ralph Baric, P. Palese. Journal of Virology, 2006

664 citations recorded by the source corpus.

Subfields: Animal Science and Zoology, Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/3d5787bf54e3970b5e6e2aef90d40de36835094c

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

1. Rolf Hilgenfeld
2. S. Weiss
3. Susanna K. P. Lau
4. Kwok-Yung Yuen
5. Ralph S. Baric
6. S. Perlman
7. Burtram C. Fielding
8. C. Machamer

In Immunology

1. R. Randall
2. Rolf Hilgenfeld
3. P. Palese
4. S. Goodbourn

In Infectious Diseases

1. Kwok-Yung Yuen
2. J. Chan
3. K. To
4. Ralph S. Baric
5. Rolf Hilgenfeld
6. Susanna K. P. Lau
7. S. Perlman
8. V. Cheng

Citations in the corpus

• Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, neutral): “For example, SARS-CoVs ORF6 can inhibit IRF3 activation and STAT1 nuclear translocation, whereas this same effect is obtained by ORF4a/b and ORF5 of MERS-CoV (Figure 5) [106,107].”
• Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor (2021, positive): “SARS‐CoV‐2 Orf6 virus‐host protein interactions Orf6 proteins from SARS-CoV and SARS-CoV-2, as expected, share functionality, including IFN-antagonistic activity [21, 28, 50] and interaction with the NUP98RAE1 complex at the nuclear pore [10, 12, 24, 25, 28].”
• Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1–Nup98 Complex to Compete With mRNA Nuclear Export (2022, background): “Although accessory proteins of SARSCoV-2 are not necessary for viral invasion and replication, they play critical roles in immune evasion (Lowery et al., 2021), as seen in other coronaviruses (Kopecky-Bromberg et al., 2007).”
• Accessory proteins of SARS-CoV and other coronaviruses (2014, background): “Protein 6 was identified as a b-interferon antagonist by Kopecky-Bromberg et al. with the intriguing finding that overexpression of p6 inhibits nuclear import of STAT1 in cells treated with IFN-b (Kopecky-Bromberg et al., 2007).”
• The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control (2020, background): “ORF3b may play a role in viral pathogenicity in addition to its inhibitory effects on interferon (IFN) expression and signaling [63,64].”
• Coronavirus Structural Proteins and Virus Assembly (2008, background): “Additionally, it was recently shown that the N proteins of both mouse hepatitis virus (MHV)-A59 and SARS-CoV are type I interferon antagonists (84, 202).”
• Coronavirus infections and immune responses (2020, background): “[47] [48] [49] It is reported that EV71 infection downregulates JAK1, p-JAK1, and p-TYK2, inhibits p-STAT1/2, and blocks the JAK-STAT signaling pathway mediated by type I IFNs, thereby hindering the function of IFNs and promoting EV71 replication and proliferation in host cells.”
• Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan (2020, background): “Orf3b was also shown to inhibit expression of IFN-β at synthesis and signalling [21] .”
• The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis (2012, background): “Suppresses the induction of type 1 IFN and IFN signaling pathways [68,94]”
• The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease (2020, background): “The related SARS-CoV virus open reading frame (ORF) and N proteins, act as antagonists to the interferon pathway by regulating IFN-β synthesis and signalling [36] which was mirrored in another experimental model [37] .”
• Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19 (2020, background): “Orf6, also antagonize IFN synthesis and signaling [23].”
• Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19 (2020, neutral): “For the closely relatedSARS-CoV-1, IFN antagonismhasbeenattributed toORF3B,ORF6, and thenucleocapsid (N) gene products (Frieman et al., 2010; Kopecky-Bromberg et al., 2007).”