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

ABSTRACT: Evidence has indicated that viral infection increases the risk of developing asthma. Although the association of human parvovirus B19 (B19V) or human bocavirus (HBoV) with respiratory diseases has been reported, little is known about the influence of the B19V-VP1u and HBoV-VP1u proteins on the symptoms of asthma. Herein, we investigated the systemic influence of subcutaneously injected B19V-VP1u and HBoV-VP1u recombinant proteins in an OVA-sensitized asthmatic mouse model. A significantly higher Penh ratio and IgE level were detected in the serum, bronchoalveolar lavage fluid (BALF) and the supernatant of a lymphocyte culture from mice treated with HBoV-VP1u or B19V-VP1u than in a lymphocyte culture from OVA-sensitized mice. Significantly higher levels of serum and BALF IgE, total IgG, IgG1, OVA-specific IgE and OVA-specific IgG1 were detected in mice treated with HBoV-VP1u or B19V-VP1u than in OVA-sensitized mice. Conversely, a significantly lower IgG2a level was detected in mice from the HBoV-VP1u or B19V-VP1u groups than in mice from the OVA group. The mice treated with HBoV-VP1u or B19V-VP1u exhibited more significant lung inflammatory indices, including elevated serum and BALF IL-4, IL-5, IL-10 and IL-13 levels; BALF lymphocyte, neutrophil and eosinophil counts, MMP-9 and MMP-2 activity; and the amount of lymphocyte infiltration, relative to those in the control mice or in those sensitized with OVA. These findings demonstrate that the subcutaneous injection of HBoV-VP1u or B19V-VP1u proteins in OVA-sensitized mice result in elevated asthmatic indices and suggest that human parvoviruses may increase the risk of developing airway inflammation in a mouse model of asthma.

SUBMITTER: Chiang SR

PROVIDER: S-EPMC6516678 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Chiang Shyh-Ren SR Lin Chia-Yun CY Chen Der-Yuan DY Tsai Hui-Fang HF Lin Xin-Ci XC Hsu Tsai-Ching TC Tzang Bor-Show BS

PloS one 20190514 5

Evidence has indicated that viral infection increases the risk of developing asthma. Although the association of human parvovirus B19 (B19V) or human bocavirus (HBoV) with respiratory diseases has been reported, little is known about the influence of the B19V-VP1u and HBoV-VP1u proteins on the symptoms of asthma. Herein, we investigated the systemic influence of subcutaneously injected B19V-VP1u and HBoV-VP1u recombinant proteins in an OVA-sensitized asthmatic mouse model. A significantly higher ...[more]

PMID: 31086415

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Project description:A unique region of human parvovirus B19 virus‑VP1 (B19V‑VP1u) has been linked to a variety of cardiac disorders. However, the precise role of B19V‑VP1u in inducing cardiac injury remains unknown. The present study investigated the effects of B19V‑VP1u and different regions of B19V‑VP1u, including B19V‑VP1uA (residues 1‑60), B19V‑VP1uB (residues 61‑129), B19V‑VP1uC (residues 130‑195) and B19V‑VP1uD (residues 196‑227), on inducing cardiac injury in naïve mice by zymography, immunoblotting, H&E staining and cytokine immunoassay. A significantly higher MMP‑9/MMP‑2 ratio and increased levels of inflammatory cytokines, including IL‑6 and IL‑1β, were detected in the left ventricles of the mice injected with B19V‑non‑structural protein 1 (B19V‑NS1) and B19V‑VP1u, accompanied by increased expression levels of phosphorylated (p‑)ERK and p‑P38. Significantly upregulated expression levels of atrial natriuretic peptide (ANP), heart‑type fatty acid‑binding protein (H‑FABP) and creatine kinase isoenzyme‑MB (CK‑MB), which are well‑known cardiac injury markers, as well as increased infiltration of lymphocytes, were detected in the left ventricles of the mice injected with B19V‑VP1, B19V‑NS1 and B19V‑VP1u. Moreover, a significantly higher MMP‑9/MMP‑2 ratio and increased levels of IL‑6 and IL‑1β were observed in the left ventricles of the mice injected with B19V‑VP1u, B19V‑VP1u‑A, B19V‑VP1u‑B and B19V‑VP1u‑C, accompanied by upregulated p‑ERK and p‑P38 expression. Notably, significantly lower levels of IL‑6 and IL‑1β were observed in the left ventricles of the mice injected with B19V‑VP1uD. Furthermore, significantly increased ANP, H‑FABP and CK‑MB expression levels were detected in the left ventricles of the mice injected with B19V‑VP1u, B19V‑VP1u‑A and B19V‑VP1u‑B, along with enhanced infiltration of lymphocytes. Significantly higher serum IL‑1β, IL‑6, TNF‑α and IFN‑γ levels were also detected in the mice injected with B19V‑VP1u, B19V‑VP1u‑A and B19V‑VP1u‑B. To the best of our knowledge, the findings of the present study were the first to demonstrate that the N‑terminal region (residues 1‑129) of B19V‑VP1u induces an increase in the levels of cardiac injury markers, thus providing evidence for understanding the possible functional regions within B19V‑VP1u.

Project description:Human parvovirus B19 (HPV B19) is pathogenic to human, which can cause fifth disease, transient aplastic crisis, arthritis, myocarditis, autoimmune disorders, hydrops fetalis, and so on. Currently, no approved vaccines or antiviral drugs are available against HPV B19, and thus the development of effective vaccines is needed. The capsid of HPV B19 is composed of two types of proteins, i.e., the major capsid protein VP2 and the minor protein VP1. Previous experimental studies have shown that the dominant immune responses against HPV B19 are elicited by VP1, especially the unique region on the N-terminus of VP1. It has been found that VP2 alone or VP2 and VP1 together can assemble into virus-like particle (VLP). The VLP structure formed by VP2 has been resolved, however, the location of VP1 in the capsid, especially the location of VP1 unique region with strong immunogenicity, is still not clear. In the present work, using the Hansenula polymorpha expression system developed by our laboratory, two kinds of recombinant HPV B19 VLPs were expressed, i.e., the VLP co-assembled by VP1 and VP2 (VP1/VP2 VLP) and the VLP whose VP1 content was improved (VP1h/VP2 VLP). The expression, purity, and morphology of these two VLPs were characterized, and then their immunogenic properties were investigated and compared with those of the VLP containing VP2 alone (VP2 VLP) previously developed by our group. Furthermore, the location of the VP1 unique region in the VLPs was determined by using the immunogold electron microscopy (IGEM). Our experimental results show that the VP1h/VP2 VLP elicits a stronger neutralization against the HPV B19 than VP2 and VP1/VP2 VLPs, which implies that the increase of VP1 content significantly improves the level of neutralizing antibodies. In addition, the IGEM observations suggest that the unique region of VP1 may be located inside the recombinant VLP. The VLPs recombinantly expressed by our Hansenula polymorpha system may serve as a promising candidate immunogen for HPV B19 vaccine development.

Dataset Information

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

Publications

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

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