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PubMed2006

Clinical aspects of parvovirus B19 infection.

Parvovirus B19 is a significant human pathogen that causes a wide spectrum of clinical complications ranging from mild, self-limiting erythema infectiosum in immunocompetent children to lethal cytopenias in immunocompromised patients and intrauterine foetal death in primary infected pregnant women. The infection may also be persistent and can mimic or trigger autoimmune inflammatory disorders. Another important clinical aspect to consider is the risk of infection through B19-contaminated blood products. Recent advances in diagnosis and pathogenesis, new insights in the cellular immune response and newly discovered genotypes of human parvoviruses form a platform for the development of modern therapeutic and prophylactic alternatives.

Autoimmune Diseases↗
PubMed2005

Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients.

Human parvovirus B19 (B19) infection has been known to cause chronic anemia, pure red cell aplasia (PRCA), glomerulopathy, and allograft dysfunction in kidney transplant (KT) recipients. The aim of this study was to evaluate the incidence and clinical significance of B19 infection in KT recipients. A total of 537 serum samples from 167 KT recipients were included in the present study. The incidence of B19 infection was based on either qualitative polymerase chain reaction (PCR) or quantitative PCR with LightCycler Parvovirus B19 Quantitation kit. Clinical significance of B19 infection was investigated by a retrospective review of hemoglobin (Hb) levels and the results of kidney and bone marrow biopsies. The overall PCR positive rate was 18.3% (98/537), and 52 of 167 (31.1%) KT recipients showed at least one positive PCR. In addition, 20 of 167 subjects (12.0%) showed PCR-positivity more than two consecutive times, and they had significantly lower Hb levels than those with negative or one positive PCR (p < 0.0001). Furthermore, two patients suffered from PRCA, which was confirmed by bone marrow biopsy. However, B19 infection did not seem to affect the graft outcome. In conclusion, the B19 infection in KT recipients was not uncommon and was associated with low Hb levels and PRCA after KT.

Adult↗
PubMedDate not supplied

Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence.

Since conducting follow-up studies of patients with acute symptomatic parvovirus B19 infection which showed that a significant proportion of patients develop prolonged arthritis and chronic fatigue syndrome (CFS), we have become interested in the mechanisms of this phenomenon. We showed that these cases have high levels of pro-inflammatory cytokines in their circulation and that this correlates with the symptoms. However, the underlying mechanisms were not apparent, and we have used various approaches to begin studying this phenomenon. DNA polymorphisms were looked for and several were shown to be more common in these subjects compared with controls; these occur within genes of both the immune response [human leucocyte antigen (HLA)-DRB1, HLA-B, transforming growth factor (TGF)-beta1] and those involved in several other cellular functions (predominantly the cytoskeleton and cell adhesion). Interestingly, one particular single-nucleotide polymorphism (SNP) which is associated with symptomatic B19 infection occurs in the Ku80 gene which has recently been shown to be a B19 co-receptor. B19 persistence is probably the key to this phenomenon, and some new data are presented on short regions of sequence homology (17-26 bp) between human, mouse and rat parvoviruses and their respective hosts which occur in many host genes. This homology may provide a foothold for virus persistence and may also play a role in the genesis of disease through gene disruption. Finally, we used microarrays and TaqMan real-time polymerase chain reaction in 108 normal persons to study human gene expression in persons who are B19-seropositive versus B19-seronegative (age- and sex-matched) to examine the hypothesis that gene regulation may be altered in subjects harbouring the B19 virus DNA. Six genes were found to be differentially expressed with roles in the cytoskeleton (SKIP, MACF1, SPAG7, FLOT1), integrin signalling (FLOT1, RASSF5), HLA class III (c6orf48), and tumour suppression (RASSF5). These results have implications not only for B19 but also for other persistent viruses as well and confirmation is required. In conclusion, these disparate findings contribute to our understanding of the pathogenesis of B19 disease. We are using these studies as a starting point to study the phenomenon of chronic immune activation following B19 infection.

Genetic Predisposition to Disease↗
PubMedDate not supplied

CD4(+) T-cell responses against the VP1-unique region in individuals with recent and persistent parvovirus B19 infection.

To date cellular immune responses against parvovirus B19 (B19) have not been studied extensively. The aim of this study was to examine the T-cell response against the VP1-unique region as the immunodominant part of the viral structural protein VP1 in individuals with different courses of B19 infection. Therefore, a group of 13 parvovirus-positive probands was separated into subgroups characterized for recent or acute, past or persistent infection by means of the presence of specific immunoglobulin (Ig)M and IgG isotypes and of viral DNA in blood and tissue. Transiently transfected B-cells expressing VP1-unique region were used in ELISpot assays to investigate T-cell responses directed against the VP1-unique region in peripheral blood mononuclear cells (PBMC) of individual donors. Significant numbers of interferon-gamma (IFN-gamma) secreting lymphocytes were detectable in PBMC of all individuals with recent, acute or persistent B19 infection, but not in PBMC of donors with past B19 infection and seronegative individuals. A more detailed analysis of IFN-gamma producing cells by intracellular cytokine staining by flow cytometry revealed, that CD4(+) T cells but not CD8(+) cytotoxic lymphocytes (CTL) were the major subpopulation of IFN-gamma producing cells. These data strongly suggest the need of virus protein production for the maintenance of VP1-unique region-specific CD4(+) T-helper cell responses in B19-infected individuals.

Antibodies, Viral↗
PubMedDate not supplied

Human parvovirus B19: a new emerging pathogen of inflammatory cardiomyopathy.

The human parvovirus B19 (PVB19), an erythrovirus causing diverse clinical manifestations ranging from asymptomatic or mild to more severe outcomes such as hydrops fetalis, is the only known human pathogenic parvovirus so far. Although enteroviruses have long been considered the most common cause of inflammatory cardiomyopathy, PVB19 is emerging as a important candidate. Recent studies have indicated an association of PVB19 with paediatric and adult inflammatory cardiac disease. However, whether or not PVB19 has an impact on inflammatory cardiomyopathy in adult patients is still unclear. The first hints for a possible aetiopathogenetic role of the PVB19-infection and the development of cardiac dysfunction were demonstrated by molecular biology utilizing in situ hybridization (ISH) and polymerase chain reaction (PCR). According to available evidence, PVB19-associated inflammatory cardiomyopathy is characterized by infection of endothelial cells of small intracardiac arterioles and venules, which may be associated with endothelial dysfunction, impairment of myocardial microcirculation, and penetration of inflammatory cells into the myocardium.

Cardiomyopathy, Dilated↗
PubMedDate not supplied

An annotated historical account of canine parvovirus.

A brief annotated history of canine parvovirus-type 2 (CPV-2) and its variants is summarized with emphasis on the most significant contributions of individuals involved in the initial recognition of CPV-2 and subsequent discoveries that have advanced our knowledge of the nature and evolution of this novel canine virus. Time has obscured the observations of many veterinary clinicians and researchers throughout the world who sensed the presence of a new disease when CPV-2 first made its appearance in 1978 and then, within 1-2 years, spread worldwide. Since 1979, nearly 600 articles, papers, numerous text chapters and monographs have been published on the subject of CPV-2. The early history is well known by veterinary infectious diseases specialists and noteworthy publications are recorded on the National Library of Medicine (USA) website, PubMed and in review articles. Because of the great number of publications, it is not practicable to cite them individually; however, reference is made to certain individuals, reviews and selected papers that I consider particularly relevant to the history of progress in the understanding of CPV-2 and the disease it causes. The clinical disease caused by CPV-2 and its variants, the immune response to infection or vaccines, host range and the development of practical diagnostic assays are noted in historical context. The basic biological properties and the physical, molecular and antigenic structure of CPV-2 and its variants are also discussed briefly. Finally, key players who have contributed to the antigenic and DNA sequence (evolutionary) relationships between CPV-2 and the other autonomous parvoviruses of carnivores are noted and hypotheses regarding the origin and evolution of CPV-2 and its variants are mentioned.

Animals↗
PubMedDate not supplied

Parvovirus B19 VP2-proteins produced in Saccharomyces cerevisiae: comparison with VP2-particles produced by baculovirus-derived vectors.

The capsids of human parvovirus B19 consist of two structural proteins, the minor-capsid protein VP1 and the major-capsid protein VP2. The latter which constitutes for 95% of the capsid are able to form virus-like particles (VLPs) in yeast without the presence of VP1-proteins. VP2-proteins produced in Saccharomyces cerevisiae have the capacity to form VLPs in the absence of VP1-proteins. These yeast-derived VLPs resemble native virus or recombinant VP2-VLPs produced by baculovirus systems in respect of size, molecular weight and of antigenicity as shown by antigen-capture ELISA and T-cell proliferation tests. Regarding costs, yield and ease of handling particle production in yeast represents an alternative to the recombinant baculovirus expression system which is so far the source for VP2-VLPs of human parvovirus B19.

Baculoviridae↗
PubMedDate not supplied

Pathophysiology and aetiological diagnosis of inflammatory myocardial diseases with a special focus on parvovirus B19.

Inflammatory processes induced by viral or bacterial infections are believed to be one of the major pathogenetic mechanisms in myocardial diseases. Although the reason for progression to myocardial failure is not fully understood, postulated mechanisms include persistent viral infection alone or in combination with autoimmune processes. A variety of cardiotropic viruses have been identified to elicit myocarditis, with enteroviruses and adenoviruses as the most frequent causative agents in children and adolescents. However, parvovirus B19 (PVB19) has recently emerged as another potential pathogen in adult patients associated with inflammatory heart disease. Many dimensions of inflammatory heart disease coexist while different phases of the disease progress simultaneously: phase 1 is dominated by viral infection, phase 2 by the onset of (probably) multiple autoimmune reactions, and phase 3 by the progression to cardiac dilatation without the role of an infectious agent and cardiac inflammation. Taking these mechanisms into account, screening for viral and bacterial genome by polymerase chain reaction (PCR) and detection of inflammatory infiltrates by immunohistochemistry are considered crucial for establishing an aetiological diagnosis, thereby allowing initiation of specific therapeutic strategies. In a large cohort of 3345 consecutive patients with left ventricular dysfunction evaluated over a period of 10 years, prevalence of PVB19, coxsackievirus (CVB), human cytomegalovirus (HCMV), influenza A virus and adenovirus (ADV) genome was assessed by PCR. Inflammatory infiltrates within the myocardium were detected by immunohistochemistry according to the WHF criteria and by histopathology according to the Dallas criteria of myocarditis. For control, endomyocardial samples of patients with arterial hypertension were studied. Parvovirus B19 was the most often detected virus in all patient subgroups, with positivity ranging from 17% to 33%. Except for PVB19, CVB RNA (3%), ADV (2%) and CMV (3.9%) were the most frequently detected viral genomes. Interestingly, detection of PVB19 genome was significantly correlated with inflammatory heart disease and reduced ejection fraction. Importantly, an aetiological diagnosis requires the immunohistochemical and molecular biological investigation of endomyocardial biopsies. Such an approach may change the management of these diseases in the future. One of the aims of the study was to reveal the underlying dominant pathophysiological mechanisms in a for deciding on the most approriate therapy.

Cardiomyopathy, Dilated↗
PubMedDate not supplied

Surveillance activity for canine parvovirus in Italy.

Recent identification of unusual canine parvovirus (CPV) mutants in cats and dogs suggests that CPV type 2 (CPV-2), which emerged suddenly in the late 1970s, is undergoing continual genetic and antigenic variations. A peculiarity of parvoviruses is that single-nucleotide substitutions may determine drastic phenotypic changes. The effects of either natural or artificial mutations on CPV phenotypic properties have been largely investigated, and this sets up CPV as an interesting model to study virus evolution. By monitoring the evolution of CPV-2 in Italy, we observed the onset and quick spread of a Glu-426 mutant, antigenically different from the pre-existing variants that were partially displaced within a few years of the initial identification of the new mutant. The identification of CPV-2 variants raises several questions concerning their impact on the efficacy of the current CPV-2 vaccines, based on the original CPV-2 strain that no longer exists in the field.

Animals↗
PubMedDate not supplied

Oncolytic potential of rodent parvoviruses for cancer therapy in humans: a brief review.

Summary Rodent parvoviruses are promising candidates for oncolytic virotherapy of cancer in humans because of their oncotropism (preferential killing of transformed cells) in the absence of pathogenicity. Here, we give an overview concerning the possible application of parvovirus H-1 for cancer therapy, with specific emphasis on malignant brain tumours in humans.

Animals↗
PubMedDate not supplied

Tissue distribution of two field isolates and two vaccine strains of porcine parvovirus in foetal organs after experimental infection of pregnant sows as determined by real-time PCR.

The aim of this study was to investigate the tissue distribution of two different field isolates and two vaccine strains of porcine parvoviruses (PPV) in infected piglets after transplacental infection. The viral load in 10 different foetal organs was determined by real-time polymerase chain reaction assays with SYBR Green targeting the viral VP2 gene and the genomic c-myc gene in 12 foetuses. The viral load in foetal tissues differed greatly among the different parvoviruses. Between one virulent field isolate compared with the other field isolate and the vaccine strains, the detected viral copy number differed in an order of magnitude of 10(9). The virulent isolate contained PPV in all 10 organs with viral loads varying between 10(11) and 10(15) per 10(6) cells. Concerning the other field isolate and the two vaccine strains, if PPV was detected, in most of the cases the highest viral load was found in foetal kidneys with a maximum viral load of 10(3) per 10(6) cells. Additionally, PPV was found in the heart of one foetus, in the liver and duodenum of one foetus and in the thymus of one foetus with viral loads varying between 10(2.1) and 10(3.5) per 10(6) cells. In completely mummified foetuses with no discriminable organs of foetuses infected with the vaccine strains and the less virulent isolate, PPV was present in very low amounts or even below the detection limit.

Animal Structures↗
PubMed1998

Variable presentation of parvovirus B19 in a family.

This case report of the sequential presentation of parvovirus B19 in a family describes a 38-year-old woman initially presenting with 'gloves and socks' syndrome, along with her husband and five children who were also affected. A high clinical attack rate with prolonged illness and variable clinical presentations was demonstrated, including polyarthritis, erythema infectiosum and symptoms of a respiratory tract infection. In addition, the range of syndromes and clinical features of parvovirus B19 are presented.

Adolescent↗
PubMed2006

Parvovirus B19 infection presenting as 'bathing trunk' erythema with pustules.

A 7-year-old girl presented with acute vulval erythema and pustules, associated with a petechial eruption in her flexures and over her feet. There was a mild prodromal illness and the patient was afebrile. There were minimal symptoms associated with the rash. Skin and throat swabs were negative and blood examination showed mild neutrophilia and lymphopaenia. Parvovirus B19 IgM was detected on serology and cutaneous features resolved within 4 days. This is a further case of parvovirus B19 infection presenting as a 'bathing trunk' exanthem that has unique dermatologic features, including the presence of pustules and distant petechiae.

Acute Disease↗
PubMed2005

Simultaneous occurrence of pure red cell aplasia and papular-purpuric 'gloves and socks' syndrome in parvovirus B-19 infection.

Papular-purpuric 'gloves and socks' syndrome (PPGSS) has been associated with parvovirus B-19 infection. We report a case of an adult immunocompetent male who presented with PPGSS. Bone marrow examination revealed pure red cell aplasia. Parvovirus B-19 DNA was detected by polymerase chain reaction in the patient's serum, whole blood and in the cutaneous lesions. This report illustrates the variety of clinical manifestations caused by B-19 infection, presents for the first time the concurrent appearance of pure red cell aplasia and PPGSS in the same patient and, finally, suggests that PPGSS may be due to direct lytic effect of the virus.

Adult↗
PubMed2000

Parvovirus B19 infection: association with third-trimester intrauterine fetal death.

OBJECTIVE: To identify the presence of parvovirus B19 infection as a possible cause of fetal loss in the third trimester. DESIGN: Prospective study of women experiencing third-trimester intrauterine fetal death (IUFD). SETTING: All cases of IUFD at Danderyd Hospital from 1992 to 1998. POPULATION: Ninety-three women with IUFD in 33,759 deliveries (0.3%). METHODS: Detection of B19 DNA by polymerase chain reaction (PCR) in placental and fetal tissue. Placental pathology and B19-specific immunohistochemistry. Maternal serology in consecutive samples. RESULTS: Among 93 cases of IUFD, seven (7.5%) had detectable B19 DNA in freshly-frozen placental tissue. The detection of B19 DNA in these tissues was confirmed by detection of B19 DNA in six separately stored paraffin-embedded placental tissues. No other explanations for the fetal deaths were found. None of the women had experienced any clinical signs of infection prior to fetal demise. None of the seven fetuses were hydropic. Histopathologic examination of the placentas revealed only minor abnormalities. Serology on maternal samples at birth revealed delayed or absent B19 IgG responses in five of seven cases. Two women were B19 IgG seropositive at the time of delivery but had unusual infection patterns; persistent viraemia for at least five months before birth in one case and likely persistence or re-infection by B19 in the other. CONCLUSION: In our study, 7.5% of IUFDs in the third trimester may have been caused by parvovirus B19 infection, without signs of fetal hydrops. This finding indicates that B19 PCR should be included in the routine investigation of IUFD.

Adult↗
PubMedDate not supplied

Parvovirus B19 in pregnancy.

Parvovirus B19 is a common, self-limiting, usually benign childhood virus that causes erythema infectiosum, also known as fifth disease. Acute infection in pregnancy can cause B19 infection in the fetus, leading to nonimmune fetal hydrops or fetal loss, depending on gestational age at the time of infection. Susceptibility to parvovirus B19 infection should be determined in selected pregnant women at high risk for exposure, and counseling should be provided regarding prevention, testing, and treatment options if exposed.

Erythema Infectiosum↗