Publication
Title
Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages
Author
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in differentiated macrophages. In macrophages, heparan sulphate glycosaminoglycans mediate the initial PRRSV attachment and the receptor sialoadhesin mediates both PRRSV attachment and internalization into endosomes. Upon a pH drop, PRRSV is uncoated and its genome is released from the endosomes into the cytoplasm, which allows virus replication. However, expression of heparan sulphate and sialoadhesin in non-susceptible cells only allows virus internalization, but no virus uncoating and infection, indicating that other factors are involved. In the present study, it is shown that treatment of macrophages with serum (mainly the alpha-globulin fraction) inhibited PRRSV infection without affecting attachment and internalization. Because alpha-globulins contain several protease inhibitors, macrophages were treated with different protease inhibitors to investigate the involvement of proteases in PRRSV uncoating. Treatment of macrophages with broadly active inhibitors of serine or aspartic proteases, but not cysteine- or metallo-proteases, inhibited PRRSV uncoating and infection. Further investigation using specific inhibitors indicated that the aspartic protease cathepsin E is involved during PRRSV uncoating, but did not allow identification of the serine protease involved. The involvement of cathepsin E during PRRSV uncoating was confirmed by partial co-localization of internalized PRRSV with cathepsin E. Furthermore, cathepsin E expression increased with macrophage cultivation, which was positively correlated with an increased susceptibility to PRRSV infection. Together, these data show that, in macrophages, both the aspartic protease cathepsin E and an unidentified trypsin-like serine protease are involved in uncoating of internalized PRRSV and subsequent infection.
Language
English
Source (journal)
Veterinary research. - Paris
Publication
Paris : 2008
ISSN
0928-4249
Volume/pages
39:6(2008), 14 p.
Article Reference
55
ISI
000261153000003
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 16.01.2015
Last edited 20.11.2017