Abstract
Both human parvovirus B19 (B19V) and human bocavirus (HBoV) are known to be important human pathogens of the Parvoviridae family. Our earlier investigation demonstrated that both B19V-VP1u and HBoV-VP1u have a significantly disruptive effect on tight junctions (TJs) in A549 cells, implying the essential role of parvovirus in airway infection and lung injury. However, no direct evidence that B19V-VP1u and HBoV-VP1u induce lung injury exists. The present study further investigates the induction of lung injury by B19V-VP1u and HBoV-VP1u in naïve Balb/c mice following subcutaneous injection of PBS, recombinant B19V-VP1u or HBoV-VP1u. The experimental results reveal significantly increased activity, protein expression and ratio of matrix metalloproteinase-9 (MMP-9) to MMP-2 in Balb/c mice that received B19V-VP1u or HBoV-VP1u compared to those that received PBS. Significantly higher levels of inflammatory cytokines, including IL-6 and IL-1β, and greater lymphocyte infiltration in lung tissue sections were detected in mice that received B19V-VP1u or HBoV-VP1u. Additionally, significantly increased levels of phosphorylated p65 (NF-κB) and MAPK signaling proteins were observed in lung tissue of mice that received B19V-VP1u or HBoV-VP1u compared to those of mice that received PBS. These findings demonstrate for the first time that B19V-VP1u and HBoV-VP1u proteins induce lung inflammatory reactions through p65 (NF-κB) and MAPK signaling.
Highlights
A growing body of evidence has implicated viral respiratory tract infection a predominant risk factor associated with a variety of lung illnesses, such as chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) [1]
Elevated matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase (MMP)-2 activities have been linked to numerous lung disorders
Increased activities of MMP-9 and MMP-2 were observed in lung tissue from Balb/c mice that received B19V-VP1 unique region (VP1u) or human bocavirus (HBoV)-VP1u protein than in those mice that received phosphate-buffered saline (PBS) (Fig 1A)
Summary
A growing body of evidence has implicated viral respiratory tract infection a predominant risk factor associated with a variety of lung illnesses, such as chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) [1]. B19V and HBoV are respiratory viruses, which can be transmitted through respiratory tract infection and are strongly associated with the development of various respiratory diseases such as sinusitis, pharyngitis, obstructive bronchitis, bronchopneumonia and asthma [17,18,19,20,21] These findings reveal that parvoviruses have a critical role in airway infection and the development of lung disease. The current study further investigates the induction of lung injury by B19V-VP1u and HBoV-VP1u in naïve mice following subcutaneous injection of recombinant B19V-VP1u and HBoV-VP1u proteins, with the goal of clarifying the potential involvement of human parvoviruses in the induction of lung disease
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