Article ; Online: Monitoring of S protein maturation in the endoplasmic reticulum by calnexin is important for the infectivity of severe acute respiratory syndrome coronavirus.
2012 Volume 86, Issue 21, Page(s) 11745–11753
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a ...
| Abstract | Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus. S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds. In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV. |
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| MeSH term(s) | Animals ; Calnexin/metabolism ; Cell Line ; Endoplasmic Reticulum/metabolism ; Glycosylation ; Humans ; Membrane Glycoproteins/metabolism ; Mice ; Protein Binding ; Protein Processing, Post-Translational ; SARS Virus/pathogenicity ; SARS Virus/physiology ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins/metabolism ; Virus Replication |
| Chemical Substances | Membrane Glycoproteins ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins ; spike glycoprotein, SARS-CoV ; spike protein, mouse hepatitis virus ; Calnexin (139873-08-8) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2012-08-22 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 80174-4 |
| ISSN | 1098-5514 ; 0022-538X |
| ISSN (online) | 1098-5514 |
| ISSN | 0022-538X |
| DOI | 10.1128/JVI.01250-12 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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