Function of HAb18G/CD147 in Invasion of Host Cells by Severe Acute Respiratory Syndrome Coronavirus

Abstract

To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147-antagonistic peptide (AP)-9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs.

Overexpression of HAb18G/CD147 promotes invasion and metastasis via α3β1 integrin mediated FAK-paxillin and FAK-PI3K-Ca2+ pathways

“…It has been demonstrated that elevated HAb18G/CD147 expression is correlated with the progression and invasion potential of human hepatoma cells [13,[22][23][24].…”

Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy

“…A study using unbiased yeasttwo-hybrid screening discovered that CypA bind to Nsp1 protein of SARS-CoV (Pfefferle et al, 2011) and HCoV-NL63 virus. The nucleocapsid (N) protein of SARS-CoV interacts with CypA, which mediates HAb18G/ CD147 to interact with SARS-CoV N protein, and thus helps in viral replication in 293 cells (Chen et al, 2005). Furthermore, silencing of the cellular CypA through siRNA inhibits the replication of HCoV-NL63 virus in Caco-2 cells, revealing the requirement of CypA for CoV infection (Carbajo-Lozoyaa et al, 2014).…”

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

“…The chemotaxis activity of CyPA is dependent upon its interaction with CD147, and inhibition of the CyPA/CD147 interaction with anti-CD147 mAb or CsA greatly decreases migration of immune cells to the sites of inflammation in mouse models of diseases such as acute lung injury, asthma, and rheumatoid arthritis (1, 16 -18). Moreover, CyPA/CD147 interaction also plays a role during the infection of many viruses, including HIV-1 (19), severe acute respiratory syndrome coronavirus (SARS-CoV) (20), vaccinia virus, vesicular stomatitis virus, and others (21,22). In addition, the cell surface expression of CD147 was reported to be regulated by the cytosolic CyPA (23).…”