Activation of AP-1 signal transduction pathway by SARS coronavirus nucleocapsid protein

Abstract

In March 2003, a novel coronavirus was isolated from patients exhibiting atypical pneumonia and subsequently proven to be the causative agent of the disease now referred to as severe acute respiratory syndrome (SARS). The complete genome of the SARS coronavirus (SARS-CoV) has since been sequenced. The SARS-CoV nucleocapsid (SARS-CoV N) shares little homology with other members of the coronavirus family. To determine if the N protein is involved in the regulation of cellular signal transduction, an ELISA-based assay on transcription factors was used. We found that the amount of transcription factors binding to promoter sequences of c-Fos, ATF2, CREB-1, and FosB was increased by the expression of SARS-CoV N. Since these factors are related to AP-1 signal transduction pathway, we investigated whether the AP-1 pathway was activated by SARS-CoV N protein using the PathDetect system. The results demonstrated that the expression of N protein, not the membrane protein (M), activated AP-1 pathway. We also found that SARS-CoV N protein does not activate NF-kappaB pathway, demonstrating that activation of important cellular pathways by SAS-CoV N protein is selective. Thus our data for the first time indicate that SARS-CoV has encoded a strategy to regulate cellular signaling process.

Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice

“…The three-dimensional structure of the N-terminal portion of the protein is similar to those of other RNA-binding proteins (Huang et al, 2004). The coronavirus N protein is thought to participate in the replication and transcription of viral RNA and to interfere with cell-cycle processes of host cells (Parker & Masters, 1990;Kuo & Masters, 2002;He et al, 2003). In addition, the N proteins of many coronaviruses are highly immunogenic and expressed abundantly during infection (Liu et al, 2001;Narayanan et al, 2003).…”

Crystal Structure of the Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein Dimerization Domain Reveals Evolutionary Linkage between Corona- and Arteriviridae

“…When co-expressed in animal cells, the M and E proteins are sufficient to form virus-like particles (10). The N protein interacts with the viral genome to form the ribonucleoprotein core and has been shown to be involved in viral RNA synthesis, transcriptional regulation of genomic RNA, translation of viral proteins, and budding (2,11,12).…”

“…When co-expressed in animal cells, the M and E proteins are sufficient to form virus-like particles (10). The N protein interacts with the viral genome to form the ribonucleoprotein core and has been shown to be involved in viral RNA synthesis, transcriptional regulation of genomic RNA, translation of viral proteins, and budding (2,11,12).Coronaviruses are related to arteriviruses by their similar genome organizations and viral replication mechanisms (3, 13). Recently, Coronaviridae and Arteriviridae were united to form the new order Nidovirales.…”

Recombinant Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein Forms a Dimer through Its C-terminal Domain

“…The N protein is typically 350 -450 amino acids in length, highly basic, and serine-phosphorylated, but the extent and physiological relevance of phosphorylation is unclear (11,12). In addition to its structural role, several additional functions are postulated for the N protein including viral RNA synthesis, transcription, translation, and virus budding (13)(14)(15).…”