The VP1 Unique Region of Parvovirus B19 and Its Constituent Phospholipase A2-Like Activity

Dorsch, Simone; Liebisch, Gerhard; Kaufmann, Bärbel; Landenberg, Philipp von; Hoffmann, Jörg H.; Drobnik, Wolfgang; Modrow, Susanne

doi:10.1128/jvi.76.4.2014-2018.2002

Cited by 162 publications

(131 citation statements)

References 27 publications

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“…In addition, a phospholipase A 2 -like activity has been shown to be associated with the VP1 unique region (11) and may be involved in the continuous production of leukotrienes and prostaglandins due to the persisting virus infection in the joints. Moreover, Ray and coworkers have recently shown that parvovirus B19 is capable of inducing a cartilage-invasive phenotype in normal human synovial fibroblast cultures (43).…”

Section: Discussionmentioning

confidence: 99%

“…The infectious particle is composed of the major capsid protein VP2 and the minor capsid protein VP1, which are identical except for the 227 amino acids at the amino-terminal end of VP1, the so-called VP1 unique region (9). Recently, a phospholipase A 2 -like activity has been linked to the VP1 unique region of several parvoviruses, including human parvovirus B19 (10,11). Immunoglobulins directed to this domain of the VP1 protein offer life-long protection against reinfection.…”

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confidence: 99%

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Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

Lehmann¹,

Knöll²,

Küster³

et al. 2003

Arthritis & Rheumatism

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Objective. To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases.Methods. Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG-complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR.Results. Twenty-six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n ‫؍‬ 22 [30%]) and/or the synovial fluid (n ‫؍‬ 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1-specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2-specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed lowdegree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples.Conclusion. Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age-matched controls.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

Lehmann¹,

Knöll²,

Küster³

et al. 2003

Arthritis & Rheumatism

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“…Both proteins also have a variety of other functions that are important for the viral life cycle, including the induction of cytokines and/or of phospholipase A 2 , which is an intermediate during the synthesis of the eicosanoids, prostaglandins, and leukotrienes that play an important role in inflammatory reactions and that may also lead to host cell dysfunction. 25 Therefore, PVB19 infection of the endothelium may cause endothelial dysfunction in infected patients without coronary artery disease. This dysfunction appears to reach a very high level during acute infections, mimicking the clinical phenotype of myocardial infarction.…”

Section: Pvb19 As a Cardiac Pathogenic Agentmentioning

confidence: 99%

High Prevalence of Cardiac Parvovirus B19 Infection in Patients With Isolated Left Ventricular Diastolic Dysfunction

et al. 2005

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Background-The etiology of left ventricular (LV) isolated diastolic dysfunction often remains unclear. In the present study, we report a strong association between parvovirus B19 (PVB19) genomes and isolated LV diastolic dysfunction. Methods and Results-In 70 patients (meanϮSD age, 43Ϯ11 years) admitted with exertional dyspnea and/or reduced exercise tolerance despite preserved LV systolic contractility (ejection fractionϭ68%), isolated diastolic dysfunction was clinically suspected. Patients with classic risk factors for diastolic dysfunction such as hypertension, coronary heart disease, diabetes mellitus, or pulmonary disease had been excluded. Diastolic function was assessed by echocardiography and LV and RV catheterization. Endomyocardial biopsies (EMBs) were analyzed for the presence of storage or infiltrative diseases or myocarditis, including molecular screening for cardiotropic virus genomes. In a substudy of 24 patients who reported atypical angina, coronary endothelial function was additionally investigated with a coronary Doppler flow-wire technique. In 37 of 70 patients (53%), isolated diastolic dysfunction was confirmed as the cause of their clinical symptoms. No evidence for cardiac storage or infiltrative diseases was found in these cases, but in 35 of 37 of these patients (95%), cardiotropic virus genomes were detected in EMBs (PϽ0.001). PVB19 was the most frequent pathogen in 31 of 37 patients (84%). In a subgroup of 10 patients with diastolic dysfunction and coexisting endothelial dysfunction, all 10 (100%) were PVB19 positive. Conclusions-PVB19 genomes were predominant in patients with unexplained, isolated diastolic dysfunction. A strong association with the incidence of endothelial dysfunction was obvious, consistent with the hypothesis that PVB19-induced endothelial dysfunction may be a possible pathomechanism underlying diastolic dysfunction.

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“…Interestingly, an active particle may also operate in trans allowing for escape of VP1u-deficient particles if contained in the same endosome (Farr et al, 2005). It has also been shown that parvovirus B19, the human virus that causes erythema infectiosum (fifth disease) has a VP1-unique region that contains PLA2 activity (Dorsch et al, 2002) and presumably operates in a manner similar to that described for MVM.…”

Section: Virus Escape From Endosomesmentioning

confidence: 99%

“…The relatively rapid endocytic uptake of parvoviruses appears to be followed by slower traffic along the endocytic compartments toward the nucleus. The endosomal pathway undertaken by parvoviruses appears to be complex and depends on the virus, its concentration, and likely the cell type (Dorsch et al, 2002;Mani et al, 2006;Sonntag et al, 2006;Suikkanen et al, 2003;Yuan & Parrish, 2001). Conformational alterations in capsid structure probably occur in the endosomal compartment facilitating uncoating and transport to the nucleus.…”

Section: Engulfmentmentioning

confidence: 99%

Clathrin-Associated Endocytosis as a Route of Entry into Cells for Parvoviruses

Johnson¹,

Dudleenamjil²

2012

Molecular Regulation of Endocytosis

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The VP1 Unique Region of Parvovirus B19 and Its Constituent Phospholipase A2-Like Activity

Abstract: Infection with the human parvovirus B19 usually results in a mild disease known as erythema infectiosum, or fifth disease

Cited by 162 publications

References 27 publications

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

High Prevalence of Cardiac Parvovirus B19 Infection in Patients With Isolated Left Ventricular Diastolic Dysfunction

Clathrin-Associated Endocytosis as a Route of Entry into Cells for Parvoviruses

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