Roles of spike protein in the pathogenesis of SARS coronavirus.
1. Infection with SARS coronavirus (SARS-CoV) induces a cellular stress condition known as the unfolded protein response (UPR). UPR induction is mediated primarily by viral spike (S) protein. The modulation of UPR by S protein involves activation of PERK protein kinase. Other branches of the UPR pathways controlled by IRE1 and ATF6 proteins, respectively, are not involved. 2. The protease inhibitor Ben-HCl effectively suppresses SARS-CoV infection by blocking virus entry. Viral infectivity is associated with the cleavage of S protein by the cellular protease factor Xa. 3. Two new aspects of the interaction between SARS-CoV S protein and the cell have been defined. These have important implications in the pathogenesis of SARS, providing opportunities for developing vaccines and antivirals against SARS-CoV. 4. Counteracting the UPR and targeting the cleavage of S protein with small molecule pharmaceutical agents represent two new anti-SARS-CoV strategies. 5. The receptor-binding domain of S protein delivered via adeno-associated virus can efficiently induce mucosal immunity and provide long-term protection against SARS-CoV infection.
Jin
D Y
DY
Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China. dyjin@ hkucc.hku.hk
Zheng
B J
BJ
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016503:Drug Delivery Systems; D015951:Factor Xa / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D017510:Protein Folding / Q000187:drug effects; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control; D064370:Spike Glycoprotein, Coronavirus; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects; D019892:eIF-2 Kinase / Q000378:metabolism*
D015951:Factor Xa; D008562:Membrane Glycoproteins; D011480:Protease Inhibitors; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D019892:eIF-2 Kinase; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus