Parvoviral infection of endothelial cells and stromal fibroblasts: a possible pathogenetic role in scleroderma

Magro, Cynthia M.; Nuovo, Gerard J.; Ferri, Clodoveo; Crowson, A. Neil; Giuggioli, Dilia; Sebastiani, Marco

doi:10.1046/j.0303-6987.2003.0143.x

Cited by 85 publications

(54 citation statements)

References 26 publications

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“…In that study, immune precipitation was suppressed significantly in patients who carried the C4A*Q0 allotype (27). More recently, the activated complement complex C5b-9 and the C5a receptor were detected in the microvasculature of SSc patients, both in the early and in the late stages of the disease (28,29).…”

Section: Discussionmentioning

confidence: 84%

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Xiang¹,

Matsui²,

Matsuo³

et al. 2007

Arthritis & Rheumatism

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Objective. To identify pathogenic and/or diseasespecific short peptides in sera from patients with systemic sclerosis (SSc).Methods. Serum samples from 40 patients with SSc, 30 patients with systemic lupus erythematosus, 21 patients with rheumatoid arthritis, 30 patients with osteoarthritis, and 26 healthy donors were tested. Short peptides with molecular weights of smaller than ϳ3 kd, purified from the sera by magnetic bead-based hydrophobic interaction chromatography 18, were detected and their amino acid sequences determined using matrix-assisted laser desorption ionization-time-offlight mass spectrometry. Effects of the identified peptides on fibroblasts and microvascular endothelial cells were tested using synthesized peptides and sera containing the peptides.

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Section: Discussionmentioning

confidence: 84%

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Xiang¹,

Matsui²,

Matsuo³

et al. 2007

Arthritis & Rheumatism

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“…It has been shown previously that endothelial cells are susceptible to B19V infection in vitro, with detection of low levels of NS1 and VP1 transcripts, but no evidence for a productive infection, such as an increase in B19V DNA amounts or detectable levels of VP1 or VP2 capsid proteins, was found (27). In vivo, B19V infection of endothelial cells has been demonstrated in myocardium (20) and skin (66), but again without any hints of a productive infection. However, both B19V nucleic acids and viral proteins have been detected in the fetal capillary endothelium in placental villi from a case of intrauterine fetal death caused by B19V (22).…”

Section: Discussionmentioning

confidence: 95%

Antibody-Mediated Enhancement of Parvovirus B19 Uptake into Endothelial Cells Mediated by a Receptor for Complement Factor C1q

Kietzell

Pozzuto

Heilbronn

et al. 2014

J Virol

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Despite its strong host tropism for erythroid progenitor cells, human parvovirus B19 (B19V) can also infect a variety of additional cell types. Acute and chronic inflammatory cardiomyopathies have been associated with a high prevalence of B19V DNA in endothelial cells of the myocardium. To elucidate the mechanisms of B19V uptake into endothelium, we first analyzed the surface expression of the well-characterized primary B19V receptor P antigen and the putative coreceptors ␣ 5 ␤ 1 integrins and Ku80 antigen on primary and permanent endothelial cells. The receptor expression pattern and also the primary attachment levels were similar to those in the UT7/Epo-S1 cell line regarded as functional for B19V entry, but internalization of the virus was strongly reduced. As an alternative B19V uptake mechanism in endothelial cells, we demonstrated antibody-dependent enhancement (ADE), with up to a 4,000-fold increase in B19V uptake in the presence of B19V-specific human antibodies. ADE was mediated almost exclusively at the level of virus internalization, with efficient B19V translocation to the nucleus. In contrast to monocytes, where ADE of B19V has been described previously, enhancement does not rely on interaction of the virus-antibody complexes with Fc receptors (FcRs), but rather, involves an alternative mechanism mediated by the heat-sensitive complement factor C1q and its receptor, CD93. Our results suggest that ADE represents the predominant mechanism of endothelial B19V infection, and it is tempting to speculate that it may play a role in the pathogenicity of cardiac B19V infection. IMPORTANCEBoth efficient entry and productive infection of human parvovirus B19 (B19V) seem to be limited to erythroid progenitor cells. However, in vivo, the viral DNA can also be detected in additional cell types, such as endothelial cells of the myocardium, where its presence has been associated with acute and chronic inflammatory cardiomyopathies. In this study, we demonstrated that uptake of B19V into endothelial cells most probably does not rely on the classical receptor-mediated route via the primary B19V receptor P antigen and coreceptors, such as ␣ 5 ␤ 1 integrins, but rather on antibody-dependent mechanisms. Since the strong antibody-dependent enhancement (ADE) of B19V entry requires the CD93 surface protein, it very likely involves bridging of the B19V-antibody complexes to this receptor by the complement factor C1q, leading to enhanced endocytosis of the virus.

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“…Although the association between B19 infection and acute and chronic myocarditis has been established with the identification of myocardial endothelial cells as target cells (8,16,41,44,52,82) and the role of B19 in the development of endothelial and isolated left ventricle diastolic dysfunction has been discussed (81), little is known about the pathophysiological mechanisms involved. B19 can be detected solely in endothelial cells of endomyocardial biopsy specimens of patients suffering from acute and chronic myocarditis (41).…”

Section: Discussionmentioning

confidence: 99%

Phospholipase A2 Activity-Dependent Stimulation of Ca ²⁺ Entry by Human Parvovirus B19 Capsid Protein VP1

Lupescu¹,

Bock

Lang

et al. 2006

J Virol

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Recent reports demonstrated an association of human parvovirus B19 with inflammatory cardiomyopathy (iCMP), which is accompanied by endothelial dysfunction. As intracellular Ca 2؉ activity is a key regulator of cell function and participates in mechanisms leading to endothelial dysfunction, the present experiments explored the effects of the B19 capsid proteins VP1 and VP2. A secreted phospholipase A2 (PLA2)-like activity has been located in the VP1 unique region of the B19 minor capsid protein. As PLA2 has recently been shown to activate the store-operated or capacitative Ca 2؉ channel I CRAC , we analyzed the impact of the viral PLA2 motif on Ca 2؉ entry. We cloned the VP1 and VP2 genes isolated from a patient suffering from fatal B19 iCMP into eukaryotic expression vectors. We also generated a B19 replication-competent plasmid to demonstrate PLA2 activity under the control of the complete B19 genome. After the transfection of human endothelial cells (HMEC-1), cytosolic Ca Human parvovirus B19, a nonenveloped virus of about 22 to 24 nm in diameter, is a member of the genus Erythrovirus within the family of Parvoviridae (35). B19 infection occurs frequently in humans, and this is documented by the high prevalence of specific immunoglobulin G (IgG) antibodies in young children (5% to 15%), adults (60%), and seniors older than 69 years (85%) (15). B19 is the causative agent of erythema infectiosum (fifth disease), hydrops fetalis, and transient aplastic anemia (1,86). Several studies disclosed an association between B19 and a variety of diseases (43,48,63,80), such as arthritis (56, 77), vasculitic syndromes (19, 24, 31, 80), hepatitis (27,36,38,75,85), and neurological disorders (2, 85). Specifically, B19 infections have been observed to be associated with acute and chronic myocarditis (13,16,30,44,53,(58)(59)(60)71). Moreover, the development of endothelial and isolated left ventricle diastolic dysfunction has been associated with B19 infection (81). During pregnancy, parvovirus B19 infection may cause maternal and fetal myocarditis, congenital abnormalities, stillbirth, and abortion (10, 21, 39, 61). The particularly severe course of the antenatal disease may relate to the preference of B19 for proliferating tissues (79).The cellular receptor for B19 infection has been regarded as a blood group P antigen based on the failure of B19 infection in a patient with a hereditary P antigen defect (12). The P antigen is necessary for B19 binding but not sufficient for virus entry into cells. In this regard, the ␣5␤1 integrin and the recently identified Ku80 autoantigen act as cellular coreceptors for human parvovirus B19 infection (57, 82). Therefore, target cells of B19 are mainly erythroid progenitor cells expressing high levels of P antigen as well as the coreceptors ␣5␤1 integrin and Ku80 autoantigen. However, nonerythroid cell lineages, such as fetal myocytes, follicular dendritic cells, and endothelial cells can be infected by B19 (12,28,29,57,82). We have recently localized B19 genomes in endothelial cells of my...

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Parvoviral infection of endothelial cells and stromal fibroblasts: a possible pathogenetic role in scleroderma

Cited by 85 publications

References 26 publications

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Antibody-Mediated Enhancement of Parvovirus B19 Uptake into Endothelial Cells Mediated by a Receptor for Complement Factor C1q

Phospholipase A2 Activity-Dependent Stimulation of Ca ²⁺ Entry by Human Parvovirus B19 Capsid Protein VP1

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Parvoviral infection of endothelial cells and stromal fibroblasts: a possible pathogenetic role in scleroderma

Cited by 85 publications

References 26 publications

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Antibody-Mediated Enhancement of Parvovirus B19 Uptake into Endothelial Cells Mediated by a Receptor for Complement Factor C1q

Phospholipase A2 Activity-Dependent Stimulation of Ca 2+ Entry by Human Parvovirus B19 Capsid Protein VP1

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Phospholipase A2 Activity-Dependent Stimulation of Ca ²⁺ Entry by Human Parvovirus B19 Capsid Protein VP1