Human parvovirus B19 VP1u Protein as inflammatory mediators induces liver injury in naïve mice

Virulence. 2016;7(2):110-8. doi: 10.1080/21505594.2015.1122165. Epub 2015 Dec 2.

Abstract

Human parvovirus B19 (B19V) is a human pathogen known to be associated with many non-erythroid diseases, including hepatitis. Although B19V VP1-unique region (B19-VP1u) has crucial roles in the pathogenesis of B19V infection, the influence of B19-VP1u proteins on hepatic injury is still obscure. This study investigated the effect and possible inflammatory signaling of B19-VP1u in livers from BALB/c mice that were subcutaneously inoculated with VP1u-expressing COS-7 cells. The in vivo effects of B19-VP1u were analyzed by using live animal imaging system (IVIS), Haematoxylin-Eosin staining, gel zymography, and immunoblotting after inoculation. Markedly hepatocyte disarray and lymphocyte infiltration, enhanced matrix metalloproteinase (MMP)-9 activity and increased phosphorylation of p38, ERK, IKK-α, IκB and NF-κB (p-p65) proteins were observed in livers from BALB/c mice receiving COS-7 cells expressing B19-VP1u as well as the significantly increased CRP, IL-1β and IL-6. Notably, IFN-γ and phosphorylated STAT1, but not STAT3, were also significantly increased in the livers of BALB/c mice that were subcutaneously inoculated with VP1u-expressing COS-7 cells. These findings revealed the effects of B19-VP1u on liver injury and suggested that B19-VP1u may have a role as mediators of inflammation in B19V infection.

Keywords: Human parvovirus B19 (B19V); VP1-unique region (VP1u); inflammation; liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Capsid Proteins / metabolism*
  • Chlorocebus aethiops
  • Hepatitis, Viral, Animal / immunology
  • Hepatitis, Viral, Animal / pathology*
  • Hepatitis, Viral, Animal / virology*
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Intravital Microscopy
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Parvovirus B19, Human / metabolism*
  • Parvovirus B19, Human / pathogenicity*
  • Phosphorylation
  • Transfection

Substances

  • Capsid Proteins
  • IL1B protein, mouse
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • capsid protein VP1, parvovirus B19
  • interleukin-6, mouse