The VP1 unique region of human parvovirus B19 and human bocavirus induce lung injury in naïve Balb/c mice

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.

Thrombocytosis and thrombocytopenia are markers of poor outcome in pediatric patients with community-acquired pneumonia

“…The investigators speculate that specific viral agents causing CAP may induce the production of interleukin-6, and lead to thrombocytosis. The increased release of interleukin-6 was reported during parainfluenza virus and human bocavirus infection in vitro and mice experiments [22,23]. Interleukin-6 induces and increases expression of hepatic thrombopoietin mRNA and consequential thrombocytosis.…”

The effects of human parvovirus VP1 unique region in a mouse model of allergic asthma

“…Human parvovirus B19 (B19V) and human bocavirus (HBoV) are important pathogenic parvoviruses that have been associated with a variety of human disorders [24]. Many global reports have indicated that there are associations between respiratory diseases and HBoV or B19V [10–14, 25–26]. However, the influence of B19V-VP1u and HBoV-VP1u on the development of asthmatic symptoms is still obscure.…”

“…Hence, an alternative method that can mimic the symptoms induced by human parvovirus infection was sought. Accordingly, various studies have indicated that the subcutaneous injection of recombinant B19V-VP1u proteins into mice induces myocardial injury, dilated cardiomyopathy and lung injury, which are recognized as a model for the systemic effects of parvovirus infection [14, 29]. Notably, a study of a dilated cardiomyopathy mouse model that is generated with the subcutaneous injection of B19V-VP1u reported that siderophages, known as heart failure cells, were observed in lung tissues [29].…”

“…The lung tissues of animals from each group were excised and soaked in formalin and covered with wax. Slides were prepared by deparaffinization and dehydration [14]. After passing through a series of graded alcohols (100%, 95% and 75%), the slides were then dyed with haematoxylin.…”

“…Notably, the VP1u regions of both B19V and HBoV have the motif of and exhibit activity of secreted phospholipidase (sPLA2), which is strongly associated with the ability to infect and induce inflammation in host cells [7–9]. Notably, human B19V and HBoV have been reported as respiratory viruses and are closely related to the risk of various respiratory diseases [10–14]. Many studies have also indicated that both B19V and HBoV are associated with asthma in children [10–18].…”