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RESEARCH PRODUCT
Human parvovirus B19 induced apoptotic bodies contain altered self-antigens that are phagocytosed by antigen presenting cells.
Violetta KivovichLi Ping WangKanoktip ThammasriStanley J. NaidesVarpu MarjomäkiSanna RauhamäkiArtemis FilippouLeona Gilbertsubject
Programmed cell deathScienceAntigen-Presenting CellsArthritisApoptosisAutoimmunitySpodopteraViral Nonstructural ProteinsBiologymedicine.disease_causeAutoantigensVirusautoimmuniteettiImmune toleranceAutoimmunityParvoviridae InfectionsPathogenesis03 medical and health sciences0302 clinical medicineImmune systemPhagocytosisImmune ToleranceParvovirus B19 HumanSf9 CellsHuman Parvovirus B19medicineta319AnimalsHumansAntigen-presenting cellself-antigens030304 developmental biology0303 health sciencesMultidisciplinaryQta1182RHep G2 CellsFlow Cytometrymedicine.diseaseVirology3. Good healthImmunologyMicroscopy Electron ScanningMedicineResearch Article030215 immunologydescription
Human parvovirus B19 (B19V) from the erythrovirus genus is known to be a pathogenic virus in humans. Prevalence of B19V infection has been reported worldwide in all seasons, with a high incidence in the spring. B19V is responsible for erythema infectiosum (fifth disease) commonly seen in children. Its other clinical presentations include arthralgia, arthritis, transient aplastic crisis, chronic anemia, congenital anemia, and hydrops fetalis. In addition, B19V infection has been reported to trigger autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the mechanisms of B19V participation in autoimmunity are not fully understood. B19V induced chronic disease and persistent infection suggests B19V can serve as a model for viral host interactions and the role of viruses in the pathogenesis of autoimmune diseases. Here we investigate the involvement of B19V in the breakdown of immune tolerance. Previously, we demonstrated that the non-structural protein 1 (NS 1) of B19V induces apoptosis in non-permissive cells lines and that this protein can cleave host DNA as well as form NS1-DNA adducts. Here we provide evidence that through programmed cell death, apoptotic bodies (ApoBods) are generated by B19V NS1 expression in a nonpermissive cell line. Characterization of purified ApoBods identified potential self-antigens within them. In particular, signature self-antigens such as Smith, ApoH, DNA, histone H4 and phosphatidylserine associated with autoimmunity were present in these ApoBods. In addition, when purified ApoBods were introduced to differentiated macrophages, recognition, engulfment and uptake occurred. This suggests that B19V can produce a source of self-antigens for immune cell processing. The results support our hypothesis that B19V NS1-DNA adducts, and nucleosomal and lysosomal antigens present in ApoBods created in non-permissive cell lines, are a source of self-antigens. peerReviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-01-01 | PLoS ONE |