Proteolytic cleavage of glycoprotein B is dispensable for in vitro replication, but required for syncytium formation of pseudorabies virus.
Glycoprotein B (gB) is the most conserved glycoprotein among herpesviruses and it plays important roles in virus infectivity. In most herpesviruses, including pseudorabies virus (PRV), gB is cleaved by a cellular protease into two disulfide-linked subunits. In the present study, I found that the PRV gB generated in human colon carcinoma LoVo cells, which lack the ubiquitous protease furin, remained in the uncleaved form and the virus replicated in these cells without cell fusion. The uncleaved gB was converted into its subunits after furin digestion. The virus also replicated in Madin-Darby bovine kidney cells without cell fusion in the presence of a furin inhibitor, whereas distinct syncytia were formed in the absence of the inhibitor. LoVo cells constitutively expressing furin showed cell fusion when they were infected with the virus. Penetration kinetics assays revealed that the virus carrying uncleaved gB penetrated the cells at the same rate as the virus carrying cleaved gB. These results indicate that PRV gB is cleaved by furin and that the cleavage is dispensable for virus replication in vitro. Furthermore, gB cleavage is involved in syncytium formation but not in penetration kinetics, suggesting that different mechanisms operate between cell-cell fusion and virus-cell fusion by PRV.
Okazaki
Katsunori
K
Department of Immunology and Microbiology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan.
D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D045683:Furin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects / Q000821:virology; D011558:Herpesvirus 1, Suid / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013552:Swine; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D015842:Serine Proteinase Inhibitors; D014759:Viral Envelope Proteins; C070915:glycoprotein gII, pseudorabies virus; D045683:Furin