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The Effect of a Unique Region of Parvovirus B19 Capsid Protein VP1 on Endothelial Cells.

ABSTRACT: Parvovirus B19 (B19V) is a widespread human pathogen possessing a high tropism for erythroid precursor cells. However, the persistence or active replication of B19V in endothelial cells (EC) has been detected in diverse human pathologies. The VP1 unique region (VP1u) of the viral capsid has been reported to act as a major determinant of viral tropism for erythroid precursor cells. Nevertheless, the interaction of VP1u with EC has not been studied. We demonstrate that recombinant VP1u is efficiently internalized by rats' pulmonary trunk blood vessel-derived EC in vitro compared to the human umbilical vein EC line. The exposure to VP1u was not acutely cytotoxic to either human- or rat-derived ECs, but led to the upregulation of cellular stress signaling-related pathways. Our data suggest that high levels of circulating B19V during acute infection can cause endothelial damage, even without active replication or direct internalization into the cells.

SUBMITTER: Rinkunaite I

PROVIDER: S-EPMC8073096 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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The Effect of a Unique Region of Parvovirus B19 Capsid Protein VP1 on Endothelial Cells.

Rinkūnaitė Ieva I Šimoliūnas Egidijus E Bironaitė Daiva D Rutkienė Rasa R Bukelskienė Virginija V Meškys Rolandas R Bogomolovas Julius J

Biomolecules 20210419 4

Parvovirus B19 (B19V) is a widespread human pathogen possessing a high tropism for erythroid precursor cells. However, the persistence or active replication of B19V in endothelial cells (EC) has been detected in diverse human pathologies. The VP1 unique region (VP1u) of the viral capsid has been reported to act as a major determinant of viral tropism for erythroid precursor cells. Nevertheless, the interaction of VP1u with EC has not been studied. We demonstrate that recombinant VP1u is efficien ...[more]

PMID: 33921883

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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 Effect of a Unique Region of Parvovirus B19 Capsid Protein VP1 on Endothelial Cells.

Publications

The Effect of a Unique Region of Parvovirus B19 Capsid Protein VP1 on Endothelial Cells.

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