Parvovirus B19 Uptake Is a Highly Selective Process Controlled by VP1u, a Novel Determinant of Viral Tropism

Leisi, Remo; Ruprecht, Nico; Kempf, Christoph; Ros, Carlos

doi:10.1128/jvi.02548-13

Cited by 58 publications

(91 citation statements)

References 36 publications

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“…37 Furthermore, a recent study reported that the VP1 unique region of human parvovirus B19 is involved in viral binding and internalization in erythroid cell lines, suggesting that VP1 of the virus can also determine viral tropism. 38 A search for the explanation of the specific tropism of parvoviruses has revealed the binding properties and functional activity of the viral receptors. Examples include some globosides and α5β1-integrin for human parvovirus B19, 39 receptor for CPV, FPV and mink enteritis virus, 41,42 and heparin sulfate, αvβ5-integrin, and growth factor receptor for adenoassociated viruses.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection

et al. 2015

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Although H-1 parvovirus is used as an antitumor agent, not much is known about the relationship between its specific tropism and oncolytic activity. We hypothesize that VP2, a major capsid protein of H-1 virus, determines H-1-specific tropism. To assess this, we constructed chimeric H-1 viruses expressing Kilham rat virus (KRV) capsid proteins, in their complete or partial forms. Chimeric H-1 viruses (CH1, CH2 and CH3) containing the whole KRV VP2 domain could not induce cytolysis in HeLa, A549 and Panc-1 cells. However, the other chimeric H-1 viruses (CH4 and CH5) expressing a partial KRV VP2 domain induced cytolysis. Additionally, the significant cytopathic effect caused by CH4 and CH5 infection in HeLa cells resulted from preferential viral amplification via DNA replication, RNA transcription and protein synthesis. Modeling of VP2 capsid protein showed that two variable regions (VRs) (VR0 and VR2) of H-1 VP2 protein protrude outward, because of the insertion of extra amino-acid residues, as compared with those of KRV VP2 protein. This might explain the precedence of H-1 VP2 protein over KRV in determining oncolytic activity in human cancer cells. Taking these results together, we propose that the VP2 protein of oncolytic H-1 parvovirus determines its specific tropism in human cancer cells.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection

et al. 2015

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“…In addition to globoside, the virus needs the binding to a specific entry receptor that triggers the endocytosis of the capsid. The membrane proteins α5β1 integrin [13] and Ku80 [14] have been proposed as possible coreceptors, however, their expression patterns only vaguely correlate with the B19V tropism and cannot explain the restricted internalization profile of the virus [5,15,16]. …”

Section: Introductionmentioning

confidence: 99%

The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells

Leisi

Nordheim

Ros

et al. 2016

Viruses

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Parvovirus B19 (B19V) is a small non-enveloped virus and known as the causative agent for the mild childhood disease erythema infectiosum. B19V has an extraordinary narrow tissue tropism, showing only productive infection in erythroid precursor cells in the bone marrow. We recently found that the viral protein 1 unique region (VP1u) contains an N-terminal receptor-binding domain (RBD), which mediates the uptake of the virus into cells of the erythroid lineage. To further investigate the role of the RBD in connection with a B19V-unrelated capsid, we chemically coupled the VP1u of B19V to the bacteriophage MS2 capsid and tested the internalization capacity of the bioconjugate on permissive cells. In comparison, we studied the cellular uptake and infection of B19V along the erythroid differentiation. The results showed that the MS2-VP1u bioconjugate mimicked the specific internalization of the native B19V into erythroid precursor cells, which further coincides with the restricted infection profile. The successful mimicry of B19V uptake demonstrates that the RBD in the VP1u is sufficient for the endocytosis of the viral capsid. Furthermore, the recombinant VP1u competed with B19V uptake into permissive cells, thus excluding a significant alternative uptake mechanism by other receptors. Strikingly, the VP1u receptor appeared to be expressed only on erythropoietin-dependent erythroid differentiation stages that also provide the necessary intracellular factors for a productive infection. Taken together, these findings suggest that the VP1u binds to a yet-unknown erythroid-specific cellular receptor and thus restricts the virus entry to permissive cells.

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“…VP1u is an N-terminal 227 amino acid long region distinguishing minor capsid component VP1 from the major VP2 protein. VP1u region possesses phospholipase activity critical for infectivity [6] and acts as a major determinant of viral tropism [7]. Upon cardiac B19V infection, viral genomes are detected only in endothelial cells and not in myocytes [2].…”

Section: Introductionmentioning

confidence: 99%

A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19

Bogomolovas

Šimoliūnas

Rinkūnaitė

et al. 2016

BioMed Research International

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Background. Parvovirus B19 (B19V) is a common finding in endomyocardial biopsy specimens from myocarditis and dilated cardiomyopathy patients. However, current understanding of how B19V is contributing to cardiac damage is rather limited due to the lack of appropriate mice models. In this work we demonstrate that immunization of BALB/c mice with the major immunogenic determinant of B19V located in the unique sequence of capsid protein VP1 (VP1u) is an adequate model to study B19V associated heart damage. Methods and Results. We immunized mice in the experimental group with recombinant VP1u; immunization with cardiac myosin derived peptide served as a positive reference and phosphate buffered saline served as negative control. Cardiac function and dimensions were followed echocardiographically 69 days after immunization. Progressive dilatation of left ventricle and decline of ejection fraction were observed in VP1u- and myosin-immunized mice. Histologically, severe cardiac fibrosis and accumulation of heart failure cells in lungs were observed 69 days after immunization. Transcriptomic profiling revealed ongoing cardiac remodeling and immune process in VP1u- and myosin-immunized mice. Conclusions. Immunization of BALB/c mice with VP1u induces dilated cardiomyopathy in BALB/c mice and it could be used as a model to study clinically relevant B19V associated cardiac damage.

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Parvovirus B19 Uptake Is a Highly Selective Process Controlled by VP1u, a Novel Determinant of Viral Tropism

Cited by 58 publications

References 36 publications

RETRACTED ARTICLE: VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection

RETRACTED ARTICLE: VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection

The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells

A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19

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