Activation of synoviocytes by the secreted phospholipase A2 motif in the VP1-unique region of parvovirus B19 minor capsid protein.
Parvovirus B19 infection in adults is often associated with acute symmetrical polyarthropathy, but the mechanism is unknown. Recently, a secreted phospholipase A(2) (sPLA(2)) motif was identified in the VP1-unique region (VP1u) of the B19 minor capsid protein. To investigate the role of this motif, we expressed VP1u with and without point mutations in the critical amino acids of sPLA(2). Although high concentrations of B19 did not infect human fibroblast-like synoviocytes (HFLSs), there was a >3-fold increase in synoviocyte migration that could be blocked by phospholipase inhibitors. Recombinant proteins with intact VP1u demonstrated sPLA(2) activity and induced cell migration, whereas proteins with mutated VP1u were nonfunctional in both assays. The incubation of HFLSs with proteins that had intact VP1u, but not with proteins with mutated VP1u, increased the production of prostaglandin E(2) >100-fold. Expression of cyclooxygenase (COX)-2 mRNA transcripts, as determined by real-time reverse-transcription polymerase chain reaction, and COX-2 protein expression were both significantly increased after incubation with protein that had intact VP1u. Proteins with VP1u in noninfectious B19 may participate in the inflammatory response in the synovial compartment.
Lu
Jun
J
Hematology Branch, National Heart, Lung, and Blood, Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Zhi
Ning
N
Wong
Susan
S
Brown
Kevin E
KE
D020816:Amino Acid Motifs; D036022:Capsid Proteins / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D054513:Group IV Phospholipases A2; D006801:Humans; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D036022:Capsid Proteins; C095547:capsid protein VP1, parvovirus B19; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2