Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB

“The N protein of SARS-CoV is 422 amino acids long, sharing only 20–30% homology with the N proteins of other coronaviruses (Marra et al., 2003; Rota et al., 2003).”

“The N protein of SARS-CoV is 422 amino acids long, sharing only 20-30% homology with the N proteins of other coronaviruses (Marra et al., 2003; Rota et al., 2003) .”

“NF-κB belongs to the Rel family of transcription factors that form homo- or heterodimers through the Rel homology domain (Akira and Kishimoto, 1997; Sen and Baltimore, 1986).”

“IL-6 is a pleiotropic cytokine that plays a major role in the host's response to injury or infection (Snick, 1990).”

“In most cells, NF-κB is present in the cytoplasm bound to a member of the IκB family of inhibitors (Verma et al., 1995; Carlotti et al., 2000).”

“IL-6 gene activation involves the rapid transport of preexisting p65 to the nucleus after release from a complex with IκB in the cytosol (Lieberman and Baltimore, 1990) .”

“Interleukin-6 (IL-6) is a pleiotropic cytokine that plays major roles in immunological responses, inflammation, bone metabolism, neoplasia, and aging (Akira et al., 1993; Papanicolaou et al., 1998; Erschler and Keller, 2000).”

“Interleukin-6 (IL-6) is a pleiotropic cytokine that plays major roles in immunological responses, inflammation, bone metabolism, neoplasia, and aging (Akira et al., 1993; Papanicolaou et al., 1998; Erschler and Keller, 2000) .”

“Interleukin-6 (IL-6) is a pleiotropic cytokine that plays major roles in immunological responses, inflammation, bone metabolism, neoplasia, and aging (Akira et al., 1993; Papanicolaou et al., 1998; Erschler and Keller, 2000).”

“…transcription factors with known consensus sequences in the IL-6 promoter region, including IRF-1 (−267 to −254), AP-1 (−283 to −277), C/EBP (−158 to −145 and −87 to −76), Sp1 (−123 to −119 and −108 to −104), and NF-κB (−75 to −63) binding sites (Akira and Kishimoto, 1992; Yan et al., 1995).”

“It has been reported that activation of IL-6 expression is controlled by the activity of several transcription factors with known consensus sequences in the IL-6 promoter region, including IRF-1 (−267 to −254), AP-1 (−283 to −277), C/EBP (−158 to −145 and −87 to −76), Sp1 (−123 to −119 and −108 to −104), and NF-κB (−7…”

“For coronaviruses, the N protein plays important roles during host cell entry and virus particle assembly and release (Hogue, 1995; Narayanan et al., 2000 Narayanan et al., , 2003 .”

“division to promote virus assembly and sequester ribosomes for translation of viral proteins (Wurm et al., 2001).”

“NF-κB belongs to the Rel family of transcription factors that form homo- or heterodimers through the Rel homology domain (Akira and Kishimoto, 1997; Sen and Baltimore, 1986).”

“NF-κB binding element is required for N protein to activate IL-6 expression Activation of the IL-6 gene relies on many consensus ciselements including NF-κB, AP-1, and C/EBP binding sites on the IL-6 promoter (Keller et al., 1996) (Fig.”

“Studies of other coronavirus have reported that the nucleocapsid proteins have a variety of functional activities (He et al., 2004).”

“The biological functions of coronavirus N protein are thought to participate in the replication and transcription of viral RNA and to interfere with the cell cycle of host cells (Parker and Masters, 1990; Kuo and Masters, 2002).”

“Two regions of N protein are essential for the viral protein to activate IL-6 gene For coronaviruses, the nucleocapsid protein plays an important role during viral packaging, viral core formation, and viral RNA synthesis (Narayanan et al., 2003).”

“In most cells, NF-κB is present in the cytoplasm bound to a member of the IκB family of inhibitors (Verma et al., 1995; Carlotti et al., 2000).”

“The SARS-CoV N protein has been reported to activate the activator protein 1 (AP1) signal transduction pathway (He et al., 2003) and to induce actin reorganization in COS-1 cells (Sutjit et al., 2004 ) by forming a dimmer by self-association (He et al., 2004) .”

“The biological functions of coronavirus N protein are thought to participate in the replication and transcription of viral RNA and to interfere with the cell cycle of host cells (Parker and Masters, 1990; Kuo and Masters, 2002).”

“The AP-1b site consensus sequence (positions −61 to −55, 5′-TGAGTCT-3′) was changed to 5′- TGCAGCT-3′ (Baccam et al., 2003).”

“The SARS-CoV N protein has been reported to activate the activator protein 1 (AP1) signal transduction pathway (He et al., 2003) and to induce actin reorganization in COS-1 cells (Sutjit et al., 2004 ) by forming a dimmer by self-association (He et al., 2004) .”

“It has been shown that the full-length sequence of NES of N protein is required for the export of the viral protein out from the nucleus (Timani et al., 2005).”

“The C/EBPb site consensus sequence (positions −86 to −76, 5′-CTTATCAAAT-3′) was changed to 5′-ACTACAAACT-3′ (Galien et al., 1996).”

“Previous studies have reported that N protein can activate transcriptional factor NF-κB and such activation is dosedependent (Liao et al., 2005).”

“The cytoplasmic localization of SARS-CoV N protein is reported recently (Chang et al., 2004) , suggesting that N protein may interact with unknown cytoplasmic and nuclear proteins to regulate host gene expression.”

“Nucleocapsid protein of SARS-CoV activates the expression of IL-6 It has been shown that high serum levels of IL-6 in the acute stage associated with lung lesions were found in SARS patients (Hsueh et al., 2004).”

“Subcloning of N gene into prokaryotic expression vector, expression and purification of N protein were described previously (Timani et al., 2004).”

“AY394850) were amplified by RT-PCR from RNA isolated previously from SARSCoV infected Vero E6 cells (Zhu et al., 2005) using corresponding primers listed in Table 2.”

“The N proteins of many coronaviruses are highly immunogenic and abundantly expressed during infection (Liu et al., 2001; Narayanan et al., 2003) .”

“This result was in agreement with the finding that through multi-alignment of total 19 sequences of the coronavirus N proteins including that of SARS-CoV, one conserved structural region at amino acids 81 to 140 was found to perform critical functions (Wang et al., 2003).”

“A similar function of N protein has been found in other viruses, in addition to coronaviruses (Myers and Moyer, 1997).”

“IL-6 plays a crucial role in autoimmune diseases because abnormally high quantities of IL-6 are found in several autoimmune diseases (Hirano, 1992) .”

“For coronaviruses, the N protein plays important roles during host cell entry and virus particle assembly and release (Hogue, 1995; Narayanan et al., 2000 Narayanan et al., , 2003 .”

“In addition to this PRR-mediated activation of NF-κ B, the nucleo-capsid protein of SARS-CoV-1 activates IL-6 expression through NF-κ B by facilitating the translocation of NF-κ B from the cytosol to the nucleus (341).”

“SARS-CoV products, such as the N protein, may directly induce IL-6 ( 55 ).”

“2007; Song et al.”

“Following in vitro analysis, Yang et al [48] suggests the use of a combination therapy for SARS-CoV or MERS-CoV, wherein a tylophorine compound known to target transmissible gastroenteritis virus and a JAK2 inhibitor synergise to block the alternative dominant NF-κB activation mediated by JAK2.”