The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

Abstract

A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.

Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements

“…The inhibition of the ISRE, IFN-β promoter, and NF-κB-RE activity, and the downregulation of the expression of IFNA1, IRF7, TLR7, MYD88, TRADD, and MAVS in the presence of each HCoV-OC43 accessory protein suggest that HCoV-OC43 ns2a and ns5a have the potential to block the type I IFN and NF-κB pathways. Previous studies have shown that SARS-CoV and MERS-CoV accessory proteins have a role in innate immune evasion [9,17,[20][21][22]. However, HCoV-OC43 accessory proteins are not homologous to SARS-CoV and MERS-CoV accessory proteins.…”

“…Uniquely, there are two accessory proteins interspaced between these structural proteins called ns2a and ns5a [8]. These proteins are not essential for replication; however, they might play a role in the pathogenesis of coronavirus infection [9].…”

Current advancements and potential strategies in the development of MERS-CoV vaccines

“…Although these accessory proteins are not essential for virus replication, recent studies by reverse genetics demonstrated that the absence of the genes encoding these proteins as a group may attenuate viral titers [23]. Additionally, the genome of MERS-CoV encodes six proteins, which are homologous to those of the known CoVs, including two replicase proteins, ORFs 1a and 1b and four major structural proteins, such as spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins (Figure 2) [11]. The E protein is a transmembrane protein forming an ion channel on the viral surface.…”

“…The transmissibility of MERS-CoV between humans is currently less efficient than that of severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged in Guangdong Province in China in 2002 and reemerged in 2004, with over 8,000 cases and more than 700 deaths in 29 countries throughout the world [10]. Nonetheless, the mortality rate for MERS (~43%) is much higher than that for SARS (~10%) [11]. It has been reported that MERS-CoV, but not SARS-CoV, could replicate in cell lines from four major chiropteran families, implying the ability of MERS-CoV in crossing species barrier between humans and bats [12].…”

Gene Therapy for Respiratory Viral Infections

“…As a CoV, SARS-CoV has a crown-like (coronal) appearance when viewed using transmission electron microscopy [58]. The spike (S) glycoprotein is embedded in the viral envelope and forms protrusions that give the characteristic appearance to the virions (Figure 9.4).…”