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J Infect Dis. 2018 Oct 22. doi: 10.1093/infdis/jiy614. [Epub ahead of print]

Parvovirus B19V Non-structural Protein NS1 Induces dsDNA Autoantibodies and End Organ Damage in Non-autoimmune Mice.

Author information

1
Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Finland.
2
Quest Diagnostics Nichols Institute, Immunology R&D, San Juan Capistrano, California, USA.

Abstract

Background:

Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) non-structural protein, NS1, a helicase, covalently modifies self dsDNA and induces apoptosis. This study tested whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model.

Methods:

BALB/c mice were inoculated with pristane, or with B19V NS1 induced or staurosporine induced ApoBods. Serum was tested for dsDNA autoantibodies by Crithidia luciliae staining and ELISA. Brain, heart, liver and kidney pathology was examined. Deposition of self-antigens in glomeruli was examined by staining with antibodies to dsDNA, histones H1 and H4, and TATA-binding protein.

Results:

B19V NS1-induced ApoBod inoculation induced dsDNA autoantibodies in a dose dependent fashion. Histopathological features of immune mediated organ damage were evident in pristane-induced and NS1-induced ApoBod groups; severity scores were higher in these groups than in staurosporine treated groups. Tissue damage was dependent on NS1-induced ApoBod dose. Nucleosomal antigens were deposited in target tissue from pristane-induced and NS1-induced ApoBod inoculated groups, but not in the staurosporine-induced ApoBod inoculated group.

Conclusions:

This study demonstrated proof of principle in an animal model that virally modified dsDNA in apoptotic bodies could break tolerance to self dsDNA and induce dsDNA autoantibodies and end-organ damage.

PMID:
30346568
DOI:
10.1093/infdis/jiy614

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