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PubMed2002

Characterization of the immune response to canine parvovirus induced by vaccination with chimaeric plant viruses.

NIH mice were vaccinated subcutaneously or intranasally with chimaeric cow pea mosaic virus (CPMV) constructs expressing a 17-mer peptide sequence from canine parvovirus (CPV) as monomers or dimers on the small or large protein surface subunits. Responses to the chimaeric virus particles (CVPs) were compared with those of mice immunized with the native virus or with parvovirus peptide conjugated to keyhole limpet haemocyanin (KLH). The characteristics of the immune response to vaccination were examined by measuring serum and mucosal antibody responses in ELISA, in vitro antigen-induced spleen cell proliferation and cytokine responses. Mice made strong antibody responses to the native plant virus and peptide-specific responses to two of the four CVP constructs tested which were approximately 10-fold lower than responses to native plant virus. The immune response generated by the CVP constructs showed a marked TH1 bias, as determined by a predominantly IgG(2a) isotype peptide-specific antibody response and the release of IFN-gamma but not IL-4 or IL-5 from lymphocytes exposed to antigen in vitro. In comparison, parvovirus peptide conjugated to KLH generated an IgG(1)-biased (TH2) response. These data indicate that the presentation of peptides on viral particles could be used to bias the immune response in favor of a TH1 response.Anti-viral and anti-peptide IgA were detected in intestinal and bronchial lavage fluid of immunized mice, demonstrating that a mucosal immune response to CPV can be generated by systemic and mucosal immunization with CVP vaccines. Serum antibody from both subcutaneously-vaccinated and intranasally-vaccinated mice showed neutralizing activity against CPV in vitro.

Administration, Intranasal↗

PubMed1997

Life-threatening anaemia caused by B19 parvovirus infection in a non-immunocompromised patient.

A 21-year-old Surinam boy suffering from a combined heterozygous sickle-cell beta-thalassaemia presented with an extreme anaemia (haemoglobin concentration 0.7 mmol/l) and severe haemolysis without signs of increased erythropoiesis. An acute B19 parvovirus infection was diagnosed by a transient increase of IgM anti-B19 parvovirus titres and a positive polymerase chain reaction for B19 parvovirus. The patient recovered spontaneously after a short period of supportive care with red cell transfusions and mechanical ventilation.

Adult↗

PubMed2001

Release kinetics and immunogenicity of parvovirus microencapsulated in PLA/PLGA microspheres.

The aim of this work was to examine the immunogenicity of microencapsulated inactivated duck parvovirus in Muscovy duck (Cairina moschata) and goose. Inactivated duck parvovirus suspension was microencapsulated into 14-17 kDa poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA50:50H) by coacervation. The in vitro antigen release from individual and mixed PLA and PLGA50:50H microspheres (MS) was biphasic with an initial lag-phase of approx. 10 days followed by a relatively constant release over additional 12 days. By varying the composition of PLA+PLGA50:50H MS mixtures from 3+1 to 1+3, the release kinetics could be altered and controlled efficiently. The antigen-loaded MS were injected subcutaneously into ducks. The immune response, expressed as virus neutralisation (VN) titres, after single administration of MS was modest, i.e. below 200 over the 6 weeks tested, unless the animals were pre-immunised 3 weeks before injecting the MS. The weak immune response was attributed to the low dose injected and inappropriate antigen release kinetics. With pre-immunised animals, however, the results were encouraging and showed that the encapsulated parvovirus was immunogenic.

Animals↗

PubMed2002

Parvovirus B19: a review.

Infection with parvovirus B19 may result in a wide range of dermatologic manifestations. The specific skin findings include erythema infectiosum and papular purpuric "gloves-and-socks" syndrome. The nonspecific findings include reticular erythema, maculopapular eruptions, and petechiae and purpura, as well as other less frequently described findings. Associations with other dermatologic diseases, such as erythema multiforme and erythema nodosum, also have been described. A role in the pathogenesis of various collagen vascular disorders has been suggested and is under investigation. The diagnosis of infection rests on the typical clinical findings. Whenever parvovirus B19 infection is diagnosed, the physician must ensure that neither the patient nor his or her contacts is a member of certain vulnerable populations. In these populations, infection with parvovirus B19 may result in devastating complications. The vulnerable populations include those with hematologic disease, immunosuppressed patients, and pregnant women. Treatment of infection in the healthy immunocompetent individual is asymptomatic, and the acute infections typically resolve without complications.

Erythema Infectiosum↗

PubMed1999

Fetal brain infection with human parvovirus B19.

Intrauterine parvovirus B19 infection is known to be one of the causes of hydrops fetalis. However, there are few reports of the pathologic changes in the central nervous system. Postmortem examination of a fetus revealed multinucleated giant cells of macrophage/microglia lineage and many small calcifications around the vessels, predominantly in the cerebral white matter. Parvovirus B19 genome DNA was detected in the nucleus of the multinucleated giant cells and solitary endothelial cells by polymerase chain reaction amplification and in situ polymerase chain reaction methods. Capsid antigen was also demonstrated in the cytoplasm of the endothelial cells by immunofluorescent assay. Thus, intrauterine B19 parvovirus infection could be associated with marked neuropathologic changes in the fetal brain at the midembryonal period. Neurologic follow-up of complications may be necessary for children who survive the intrauterine infection.

Adult↗

PubMed2002

Chronic human parvovirus B19 infection in rheumatic disease of childhood and adolescence.

Parvovirus B19 causes erythema infectiosum in children, but the virus is associated with an increasing range of different diseases. About 20% of infections are associated with delayed virus elimination and viremia persisting over several months or years. These persistent B19-infections are characterised by the presence of IgG against the non-structural protein NS1. This study aimed to find further evidence for an association of parvovirus B19 persistence with VP1/2- and NS1-specific IgG-antibodies in children suffering from rheumatic diseases of childhood. Forty-eight children and adolescents with joint complaints lasting longer than 1 year including patients with juvenile systemic sclerosis and juvenile dermatomyositis showed antibodies against the viral NS1-protein. Laboratory markers of inflammation, humoral immune response against parvovirus B19 proteins and the presence of viral genomes in patients' sera as well as in 124 healthy children were investigated. Almost 50% of the patients showed laboratory signs of chronic inflammation. B19-DNA was amplified in 31% of patients' sera and 7% of the controls (P<0.0001). VP2-specific IgM was detectable in 50% of the patients' and 6% of control sera. NS1-specific immune reactions were linked to persistent B19-infection as indicated by the presence of viral genomes in the peripheral blood and of VP2-specific IgM years after disease onset. To estimate the severity of the disease and the clinical course, the number of affected and functionally impaired joints were noted and compared with the records from patients' initial visit in the hospital. Disease related complications were registered. Impairment of activities of daily living was assessed by Childhood Health Assessment Questionnaire (CHAQ)- and Munich Quality of Life Questionnaire (KINDL)-tests. During observation the clinical state of four patients worsened, 27 improved, the others remained stable. Twenty-four children were restricted in their daily activities.

Adolescent↗

PubMed2002

Detection of human parvovirus B19 infection: a study of 212 suspected cases in the state of Rio de Janeiro, Brazil.

BACKGROUND: Parvovirus B19 infections are associated with different clinical manifestations that vary from symptom-less to severe. The main clinical manifestations are erythema infectiosum or fifth disease, transient aplastic crisis in individuals with hemoglobinopathies, chronic anemia in the immunocompromised, acute polyarthralgia syndrome in adults, hydrops fetalis, spontaneous abortion and stillbirth. Although the classical features of B19 and rubella infections are distinct, uncommon presentations can lead to misdiagnosis. OBJECTIVE: The goal of this study was to assess the occurrence of parvovirus B19 (B19) infection in patients with clinical signs of toxoplasmosis or rubella, both of which were not confirmed by laboratorial techniques. STUDY DESIGN: Serum samples from 214 patients were collected between January 1996 and December 1997 in the state of Rio de Janeiro, Brazil, B19 specific IgG and IgM were detected by using commercial enzyme-linked immunosorbent assays (ELISA), and viral nucleic acid was detected employing a nested polymerase chain reaction (PCR) protocol. RESULTS: Combining the results obtained by IgM ELISA and PCR, 14.5% of the samples were positive in one or both tests, with a concordance of 92.5% between the two techniques. CONCLUSIONS: Specimens collected in 16 out of 22 municipalities were positive in at least one out of the three tests employed, indicating that parvovirus B19 circulates in several regions of the state of Rio de Janeiro.

Abortion, Spontaneous↗

PubMed2003

Pure red cell aplasia associated with parvovirus B19 infection in a patient with ulcerative colitis.

Anemia is a common problem that results from various causes in patients with ulcerative colitis (UC), but there is little information on the association of UC with pure red cell aplasia (PRCA). We describe the first case of parvovirus-induced PRCA in UC. A 28-year-old woman with chronic UC was admitted to the hospital for treatment of active pancolitis. Three courses of pulse therapy with methylprednisolone provided complete remission. However, the patient developed reticulocytopenia and a subsequent fall in hemoglobin to 6.2 g/dl. Bone marrow examination revealed selective aplasia of red cell precursors and giant pronoromoblasts. Enzyme immunoassay identified specific immunoglobulin M antibody against parvovirus B19 in the serum. Based on these findings, the diagnosis of PRCA caused by the virus was made. The patient was treated with a 3-day course of intravenous immunoglobulin (5 g/day), resulting in brisk reticulocytosis, folowed by normalization of hemoglobin level. In conclusion, Chronic or acute blood loss in UC associated with enhanced red cell turnover might be a risk factor for PRCA when affected patients contract parvovirus B19 infection.

Adult↗

PubMed2001

Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation.

The clinical significance of parvovirus B19 infection in pediatric solid-organ and bone marrow transplanted patients is unclear. The overall prevalence of parvovirus B19 infection in these patients is about 1-2% during the first year after transplantation. The most common symptom is anemia, but leukopenia and thrombocytopenia have also been observed. Rare cases of hepatic dysfunction, myocarditis, vasculitis and respiratory failure have also been reported. Whereas serology is of limited value around the time of transplantation, it is recommended that a search for B19 DNA is included in first-line investigations in any transplanted patient with unexplained anemia. Specific antiviral therapy is not available, however, intravenous immunoglobulin produces rapid improvement in most cases. Although relatively rare, the severe complications following parvovirus B19 infection in the transplant setting can be avoided by early diagnosis and treatment.

Antibodies, Viral↗

PubMed2000

A causal role for parvovirus B19 infection in adult dermatomyositis and other autoimmune syndromes.

BACKGROUND: Infection with parvovirus B19 (B19) has been associated with connective tissue disease (CTD) stigmata, namely, a systemic lupus erythematosus (SLE)-like illness, seronegative polyarthritis resembling rheumatoid arthritis, and vasculitis. The dermatopathology and pathogenetic basis of such B19-associated CTD-like syndromes have not been elucidated. OBJECTIVE: We attempted to document persistence of the B19 genome in skin lesions of 7 patients with CTD-like symptomatology following B19 infection and to correlate systemic manifestations to dermatopathological findings. METHOD: In 7 prospectively encountered patients in whom history, clinical signs and/or serology supported a diagnosis of CTD in the setting of B19 infection, dermatopathological and clinical features were correlated. Parvovirus B19 viral genome was sought in skin tissue using the polymerase chain reaction (PCR). RESULTS: Two patients had clinical features diagnostic of myopathic dermatomyositis (DM), 1 of whom is still symptomatic 1.5 years after the onset of her illness, and the other has had typical clinical features of DM for a duration of 3.5 years. A 3rd patient with SLE remains symptomatic 4 years after the onset of her illness. A 4th patient has persistent seronegative symmetrical polyarthritis of 6 years' duration and cutaneous lesions of granuloma annulare (GA). The 5th patient has a 1.5-year history of debilitating polyarthritis and cutaneous lesions with overlap features of DM and subacute cutaneous LE (SCLE). The 6th patient has had a persistent folliculocentric necrotizing vasculitis for 3 years. The 7th patient has a 1-year history of microscopic polyarteritis nodosa (PAN) with cutaneous vasculitis and persistent active renal disease. In 4 patients, exposure to children with fifth disease immediately preceded the onset of their CTD. Parvovirus B19 infection was documented serologically in 6 patients with antibodies of IgG subclass in 6 and of IgM subclass in 1. Four of 6 patients questioned had a history of atopy. Skin biopsies from patients with clinical features of SLE or DM demonstrated an interface dermatitis with dermal mucinosis. A necrotizing vasculitis with epithelial pustulation was seen in 2 patients. Interstitial GA-like infiltrates were seen in 5 cases. Immunofluorescent (IF) testing revealed a positive lupus band test (LBT) and epidermal nuclear and vascular staining for IgG and C5b-9 in the SLE patient. One DM patient had a negative LBT in concert with C5b-9 deposition along the dermoepidermal junction (DEJ) and within blood vessels while the other showed endomysial vascular Cs5b-9 deposition. In all patients, skin biopsy material contained B19 genome, which was absent in the serum of 4 patients analyzed. Symptomatic relief followed immunosuppressive and immunomodulatory therapy with agents including prednisone, cyclophosphamide, hydroxychloroquine, non-steroidal anti-inflammatory drugs and etanercept, but no patient has had complete symptom resolution. CONCLUSIONS: Persistent B19 infection may be of pathogenetic importance in certain prototypic CTD syndromes, to which underlying immune dysregulation associated with a blunted IgM response to viral antigen may predispose. Anti-viral therapy might be worthy of consideration since traditional immunosuppressive therapy was unsuccessful in our cases.

Adult↗

PubMed2002

Parvovirus B19 associated adult Henoch Schönlein purpura.

BACKGROUND: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated. METHODS: Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies. CASE PRESENTATION: A 64-year-old-female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA-associated mesangioproliferative glomerulonephritis and IgA-associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor alpha DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells. CONCLUSION: This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19-associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti-TNFalpha therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.

DNA, Viral↗

PubMed2002

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice.

We have previously shown that the growth of human tumor xenografts in immunodeficient mice can be efficiently suppressed upon infection with the autonomous parvovirus H-1 or with cytokine-transducing derivatives thereof. To further evaluate the benefits of implementing parvoviruses in cancer gene therapy, we have created a new recombinant vector, MVMp/IP-10, transducing the immunoactive, antiangiogenic chemokine IP-10, and used this virus to treat syngeneic tumors grown in immunocompetent mice. Intratumoral/intraperitoneal administration of only 3 x 10(7) replication units of MVMp/IP-10 per animal strongly inhibited the progression of established H5V cell-induced vascular tumors, a highly malignant mouse model for human cavernous hemangioma and Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life-threatening metastatic dissemination to internal organs were accompanied by a striking delay in hemangioma-associated mortality. Parental MVMp did not have a significant effect under these conditions up to the dose of 10(10) infectious units/animal, but had strong antihemangiosarcoma activity when used to infect H5V cells ex vivo prior to implantation. In all cases, virus therapy was very well tolerated. Virus-induced suppression of hemangiosarcoma was dependent on host T cells and associated with intratumoral persistence of IFN gamma-expressing cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen activator inhibitor-1 (PAI-1), a metastasis-linked marker. This proof of principle study demonstrates that MVMp/IP-10 can aid the treatment of vascular tumors and that autonomous parvovirus-based vectors can be considered potent tools for cancer gene therapy purposes.

Animals↗

PubMed2006

Targeting of autonomous parvoviruses to colon cancer by insertion of Tcf sites in the P4 promoter.

The Wnt signaling pathway is activated by mutations in the adenomatous polyposis coli (APC) or beta-catenin genes in most colon cancers, leading to the transactivation of promoters containing binding sites for the Tcf/LEF family of transcription factors. We have previously shown that it is possible to confer colon cancer specificity on autonomous parvoviruses by inserting Tcf sites into the viral P4 promoter. The mutant Tcf promoters were responsive to activation of the Wnt pathway but the viruses replicated poorly. We show here that reduction of the number of Tcf sites from four to two leads to an increase in the efficiency of replication and toxicity of the viruses in Co115 colon cancer cells, with only a small reduction in selectivity for cells with an active Wnt signaling pathway. Despite this improvement, virus production by most colon cancer cells remained low. Analysis of parental phH1 virus infection of SW480 colon cancer cells showed that the nonstructural and capsid proteins were expressed, but single stranded DNA and progeny virus were not produced. This defect reflects the dependence of autonomous parvoviruses on host functions for many steps in their replication cycle and represents a major limitation to the use of selectively replicating parvoviruses for colon cancer therapy.

Adenomatous Polyposis Coli↗

PubMed1999

Control of parvovirus DNA replication by a tetracycline-regulated repressor.

Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The potential for systemic use of these viruses in targeting metastases might be enhanced if NS1 expression and viral replication could be controlled by an innocuous drug such as tetracycline. We therefore substituted prokaryotic tetracycline operator sequences for part of P4 of LuIII, the promoter responsible for transcription of the mRNAs for nonstructural proteins. The resulting construct unexpectedly showed constitutive expression in transiently transfected cells, as indicated by efficient excision and amplification of viral replicative form (RF) DNA. This was apparently due to self-stimulatory transcriptional transactivation by NS1. This problem was overcome by cotransfection with a plasmid expressing a chimera of the repressor of the tetracycline operon with a KRAB transrepression domain. These conditions allowed efficient control of transcription and RF amplification by the tetracycline derivative, doxycycline. These observations form a basis for developing a therapeutic agent based on a drug-controlled parvovirus.

Anti-Bacterial Agents↗

PubMed2002

Systemic lupus erythematosus associated with acute parvovirus B19 infection.

Acute parvovirus B19 infection has been implicated in the pathogenesis of several autoimmune conditions, including systemic lupus erythematosus. Viruses, including human parvovirus B19, may trigger bouts of systemic lupus erythematosus in genetically susceptible individuals. Herein, we report on two patients who developed systemic lupus erythematosus associated with acute parvovirus B19 infection and discuss the possible pathogenetic mechanisms implicated.

Acute Disease↗

PubMed2004

Oral manifestations of papular-purpuric 'gloves and socks' syndrome due to parvovirus B19 infection: the first case presented in Greece and review of the literature.

Papular-purpuric 'gloves and socks' syndrome (PPGSS) is a novel, rare, self-limited dermatosis initially described in 1990. It is characterized by painful, pruritic edema and erythema, rapidly evolving to papular-purpuric lesions on the distal extremities, in a gloves-and-socks distribution, accompanied by fever and oral lesions such as petechiae, vesiculopustules and small erosions. Parvovirus B19 has been implicated in most cases as the etiological factor. Herein we present the first case of PPGSS in a 42-year-old Greek man with von Willebrand disease. On admission the patient was febrile, and presented acral edema and erythema rapidly followed by purpuric lesions on the same sites, and palatal petechiae. Complete remission of the exanthem occurred 7 days after hospitalization. Clinical and laboratory evaluation including serologic tests and PCR, confirmed the presence of parvovirus B19. Review of the existing literature on this novel syndrome and its association with parvovirus B19 is also presented.

Adult↗

PubMed1996

Transmission of symptomatic parvovirus B19 infection by clotting factor concentrate.

The risk of acquiring diseases from transfusion of blood and blood products is well recognized and the issue of parvovirus in haemophiliacs is not a new one. We report two patients with haemophilia acquiring iatrogenic parvovirus B19 infection, resulting in life-threatening sepsis in one, and immunocompetent adult. Over the last 10 years there has been great progress in manufacturing safer products with regard to enveloped viruses such as HIV, hepatitis B and C. A recent outbreak across Europe of hepatitis A in haemophiliacs treated with plasma-derived factor VII concentrates has made haemophilic treaters concerned about the known (parvovirus B19 and hepatitis A) and the unknown non-lipid enveloped viruses that may be contained in the clotting factor concentrates, because these are resistant to the existing viral inactivating techniques. The possibility of HIV itself mutating into a non-lipid enveloped virus emphasizes the need to seek and use safer products.

Adult↗

PubMed2000

Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery.

Human parvovirus B19 infection has been shown to be transmissible by blood and blood products and to result in transient aplastic crisis in patients with rapid red cell turnover. We report three cases of iatrogenic parvovirus B19 infection resulting from the use of the same batch of fibrin sealant under operation. Fibrin sealant, which is a typical haemostatic agent produced from blood, has been used during surgery. Human parvovirus is resistant to existing virus-inactivating techniques, suggesting that infection may occur from blood products contaminated with it. Use of recombinant products for these proteins may thus be necessary.

Adult↗