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PubMed2002

T lymphocyte responses against human parvovirus B19: small virus, big response.

Parvovirus B19 elicits both humoral and cellular immune responses. Recently some advances have been made in determining the frequencies, peptide targets and function of virus-specific CD8+ T lymphocyte responses. A single HLA B35-restricted epitope derived from the NS1 protein has been studied so far, but others clearly exist. Surprisingly large, persistent responses have been detected in healthy seropositive individuals, using interferon-gamma ELISpot assays and HLA class I peptide tetramers. Similar techniques are available for exploration of the CD4+ T cell epitopes, although less detail is currently available. Mapping of cellular immune responses against the entire B19 genome (the parvovirus "immunome") is now possible and if similarly large populations are found consistently, this could yield important insight into normal immunological control and abnormalities in B19-related disease.

Antigens, Viral↗
PubMed2000

Molecular characterization of canine parvovirus in Brazil by polymerase chain reaction assay.

Canine parvovirus (CPV) was first isolated in 1978 in the USA. Analysis of CPV isolates by monoclonal antibodies and restriction enzymes have shown that after the first emergence of CPV (CPV-2) it evolved to give rise to new antigenic types, which were designated CPV type 2a and type 2b. These new types have replaced the original CPV type 2, although the proportions of each of the new antigenic types vary in different countries. In Brazil, CPV-like infections were first observed in 1979, however, there has been no information concerning the antigenic types of CPV prevailing in South America. In this study, we designed a PCR assay to type canine parvovirus strains in fecal samples collected from symptomatic dogs during 1980 through 1986 and 1990 through 1995. Our data showed that the CPV epizootic in Brazil followed the same pattern observed in the USA of emergence of CPV-2 followed by replacement by the variants CPV-2a and 2b. The predominant strain found during 1980 was CPV-2a, which was substantially replaced by CPV-2b from 1990 to 1995.

Animals↗
PubMed2003

Case of stroke in a 7-year-old male after parvovirus B19 infection.

A 7-year-old male presented sudden-onset left hemiparesis, left-sided paresthesia, central paralysis of the left VII cranial nerve, and subsequent headache. Magnetic resonance scans were obtained 24 hours after admission. T(2)-weighted images disclosed hyperintensities located mainly in the posterior portion of the lenticular nucleus and in the head and body of the right caudate nucleus. A diagnosis of ischaemic stroke was made on the basis of neuroradiologic findings. Laboratory tests undertaken to establish the cause of stroke revealed parvovirus B19 infection preceding the neurologic abnormalities. In the absence of other known risk factors for stroke the possibility of parvovirus B19's being correlated with stroke onset is discussed.

Child↗
PubMed1998

Rheumatic manifestations of parvovirus B19 infection.

Human parvovirus B19 is an emerging DNA virus. B19 infection is common and widespread. Major manifestations of B19 infection are transient aplastic crisis, erythema infectiosum, hydrops fetalis, acute and chronic rheumatoid-like arthropathy, and, in the immunocompromised host, chronic or recurrent bone marrow suppression. A number of less common manifestations of B19 infection include various rash illnesses, neuropathies, and acute fulminant liver failure. Of rheumatologic interest, B19 infection must be differentiated from early presentation of more classic erosive rheumatoid arthritis and, in some cases, systemic lupus erythematosus. It is unlikely that B19 plays a role in classic erosive rheumatoid arthritis, but understanding pathogenesis of B19 arthropathy may provide insights into the mechanisms by which rheumatoid arthritis develops. Evidence for persistence of B19 infection suggests that human parvovirus B19 infection may serve as a model for the study of virus-host interactions and the role of viruses in the pathogenesis of rheumatic diseases.

Diagnosis, Differential↗
PubMed1995

B19 parvovirus.

B19 parvovirus is pathogenic in man and causes a variety of clinical illnesses, among them several haematological diseases. Acute infection of a host with underlying haemolysis produces transient aplastic crisis; of the midtrimester fetus, hydrops fetalis; and of an immunocompromised patient, pure red cell aplasia. The target of B19 parvovirus infection is the human erythroid progenitor cell. Infection is cytotoxic due to expression of the viral nonstructural protein. The virus can be propagated in cultures of human bone marrow, blood, and fetal liver. Humoral immunity normally terminates infection, and commercially available immunoglobulin can be used to treat persistent infection. Recombinant capsids, produced in a baculovirus system, are suitable as a vaccine reagent.

Adult↗
PubMed1995

Pathogenesis of feline panleukopenia virus and canine parvovirus.

Feline panleukopenia virus (FPV) and canine parvovirus (CPV) are autonomous parvoviruses which infect cats or dogs, respectively. Both viruses cause an acute disease, with virus replicating for less than seven days before being cleared by the developing immune responses. The viruses have a broad tropism for mitotically active cells. In neonatal animals the viruses replicate in a large number of tissues, and FPV infection of the germinal epithelium of the cerebellum leads to cerebellar hypoplasia, while CPV may infect the hearts of neonatal pups, causing myocarditis. In older animals the virus replicates systemically, primarily in the primary and secondary lymphoid tissues, and also in the rapidly replicating cells of the small intestinal epithelial crypts. A transient panleukopenia or relative lymphopenia is often observed after FPV or CPV infection, respectively. Whether the reduction in cell numbers in vivo is due to virus replicating in and killing cells, or due to other indirect effects, is not known. However, FPV kills both erythroid and myeloid colony progenitors in in vitro bone marrow cultures, and it has been suggested that virus replication in the myeloid cells in vivo could lead to the reduced neutrophil levels seen after FPV infection of cats.

Animals↗
PubMed1994

The structure of a neutralized virus: canine parvovirus complexed with neutralizing antibody fragment.

BACKGROUND: Members of the Parvovirus genus cause a variety of diseases in mammals, including humans. One of the major defences against viral infection is the presence of neutralizing antibodies that prevent virus particles from infecting target cells. The mechanism of neutralization is not well understood. We therefore studied the structure of canine parvovirus (CPV) complexed with the Fab fragment of a neutralizing antibody, A3B10, using image reconstruction of electron micrographs of vitrified samples, together with the already known structure of CPV from X-ray crystallographic data. RESULTS: The structure of the complex of CPV with Fab A3B10 has been determined to 23 A resolution. The known CPV atomic structure was subtracted from the electron density of the complex, and the difference map was used to fit the atomic coordinates of a known Fab fragment, HyHEL-5. The long axis of each Fab molecule is oriented in a near radial direction, inclined away from the two-fold axes. The viral epitope consists of 14 amino acid residues found in loops 1, 2 and 3 on the capsid surface, which include previously identified escape mutations. CONCLUSIONS: The mode of Fab binding suggests that the A3B10 neutralizing antibody cannot bind bivalently to the capsid across the two-fold axes, consistent with the observation that whole A3B10 antibody readily precipitates CPV. Since Fab A3B10 can also neutralize the virus, mechanisms of neutralization such as interference with cell attachment, cell entry, or uncoating, must be operative.

Amino Acid Sequence↗
PubMed1995

Single-stranded DNA-protein interactions in canine parvovirus.

BACKGROUND: Parvoviruses are small icosahedral single-stranded (ss) DNA viruses which replicate in rapidly proliferating cells, causing a variety of serious and often lethal diseases in mammals, including humans. The structure of canine parvovirus (CPV) showed an 11-nucleotide oligomeric fragment of its genome bound to 60 equivalent binding sites on the inside surface of the capsid. This provides an opportunity to study the conformation of ssDNA, its interactions with protein, and its role in viral assembly. RESULTS: The icosahedrally ordered part of CPV ssDNA has an unusual loop conformation with the bases pointing outwards and the phosphates surrounding metal ions on the inside. The protein interacts with the bases, making 15 putative hydrogen bonds. The DNA electron density indicates preferences for particular base types in parts of the binding site. Statistical analysis of the genome yields approximately 30 regions with sequences similar to that observed in the structure, demonstrating a low level of sequence specificity for binding to capsid protein. CONCLUSIONS: ssDNA can adopt unusual conformations upon association with protein by using phosphoribose backbone rotamers that are found in tRNA, but not in DNA duplexes. The CPV DNA-protein interactions differ from the non-specific backbone interactions seen in some plant and insect viruses. The sequence specificity, albeit low level, of the protein for CPV DNA may contribute both to distinguishing the viral DNA from other nucleic acids and to the DNA packaging process during viral assembly.

Amino Acids↗
PubMed2002

Autonomous parvovirus vectors.

Parvoviruses are small, icosahedral viruses (approximately 25 nm) containing a single-strand DNA genome (approximately 5 kb) with hairpin termini. Autonomous parvoviruses (APVs) are found in many species; they do not require a helper virus for replication but they do require proliferating cells (S-phase functions) and, in some cases, tissue-specific factors. APVs can protect animals from spontaneous or experimental tumors, leading to consideration of these viruses, and vectors derived from them, as anticancer agents. Vector development has focused on three rodent APVs that can infect human cells, namely, LuIII, MVM, and H1. LuIII-based vectors with complete replacement of the viral coding sequences can direct transient or persistent expression of transgenes in cell culture. MVM-based and H1-based vectors with substitution of transgenes for the viral capsid sequences retain viral nonstructural (NS) coding sequences and express the NS1 protein. The latter serves to amplify the vector genome in target cells, potentially contributing to antitumor activity. APV vectors have packaging capacity for foreign DNA of approximately 4.8 kb, a limit that probably cannot be exceeded by more than a few percent. LuIII vectors can be pseudotyped with capsid proteins from related APVs, a promising strategy for controlling tissue tropism and circumventing immune responses to repeated administration. Initial success has been achieved in targeting such a pseudotyped vector by genetic modification of the capsid. Subject to advances in production and purification methods, APV vectors have potential as gene transfer agents for experimental and therapeutic use, particularly for cancer therapy.

Animals↗
PubMed2002

Presence of parvovirus B19 DNA in chronic urticaric and healthy human skin.

BACKGROUND: The etiology of chronic urticaria is undefined, but the potential role of infectious agents as one triggering factor has been suggested. The appearance of chronic urticaria in a 16-year old male after a history of a recent parvovirus B19 (B19) infection led us to investigate the association between B19 and chronic urticaria. OBJECTIVES: To investigate whether parvovirus B19 (B19) has a role in chronic urticaria. STUDY DESIGN: We amplified B19 DNA from skin biopsy samples of 36 adult chronic urticaria patients as well as of 22 healthy controls using two sets of separate primers and probe. Circulating IgG and IgM antibodies to B19 were measured from 27 patients and from all controls. RESULTS: B19 DNA was detected in 18 (50%) skin biopsy samples of 36 patients with chronic urticaria. Unexpectedly, also 14 (64%) skin biopsy samples from 22 healthy controls harbored B19 DNA. All 32 persons with positive B19 PCR findings had circulating IgG-class antibodies to B19 major structural protein VP2, but no IgM antibodies. CONCLUSION: Our results show that B19 DNA commonly exists in human skin. Therefore, the association between B19 infection and chronic urticaria remains uncertain. However, these findings raise the question whether the skin may constitute a reservoir for B19.

Adolescent↗
PubMed2003

Parvovirus B19 infection and autoimmune disease.

Human parvovirus B19 infections may cause a widespread benign and self-limiting disease in children and adults, known as erythema infectiosum or fifth disease. A variety of further manifestations are associated with the infection such as arthralgias, arthritis, leukopenia and thrombocytopenia, anemia and vasculitis, spontaneous abortion and hydrops fetalis in pregnant women. Both in children and adults parvovirus B19 infections have been frequently implicated as a cause or trigger of various forms of autoimmune diseases affecting joints, connective tissue and large and small vessels. In addition, autoimmune neutropenia, thrombocytopenia and hemolytic anemia are known as sequelae of B19 infection. The molecular basis of the autoimmune phenomena and resultant pathogenesis is unclear. The involvement of molecular mimicry between cellular and viral proteins, the induction of enhanced cytokine production via the viral transactivator protein NS1 and the phospholipase A2-like activity of the capsid protein VP1 may contribute to the induction of autoimmune reactions. All the known data and the potential mechanisms involved in the pathogenesis will be discussed in this review.

Autoimmune Diseases↗
PubMed2006

Childhood chorea-encephalopathy associated with human parvovirus B19 infection.

An 8-year-old female presented with a distinct clinical course characterized by an acute self-limiting chorea-encephalopathy with cerebrospinal fluid (CSF)-specific oligoclonal bands. During the clinical course, genomic human parvovirus B19 DNA was detected in her serum and CSF. It was concluded that this patient represents the first published case of childhood chorea-encephalopathy associated with, and probably caused by, human parvovirus B19 infection.

Brain Diseases, Metabolic↗
PubMed1994

Low prevalence of antibody to human parvovirus B19 in Singapore.

A seroepidemiological survey was conducted in Singapore to assess the prevalence of antibody to human parvovirus B19. Sera were collected from 600 healthy individuals between 6 months and over 50 years of age and tested for IgG antibody against B19 virus by antigen capture indirect immunosorbent assay. The overall seropositivity rate was 16.2%. All the children under 5 years of age were seronegative. Antibody prevalence increased gradually from 3.5% in school children (5-14 years of age) to 7.7% in age group 15-19 years and then to 10.3% in young adults (20-24 years of age). In the age group 25-34 years the prevalence was 28% and in the age group over 35 years 65% had parvovirus B19 antibody. The results of the survey indicate that there has been very low incidence of B19 virus infection in Singapore during the last two decades.

Adolescent↗
PubMed2002

Seroprevalence of parvovirus B19 in urban Chilean children and young adults, 1990 and 1996.

An immunofluorescence test for detecting parvovirus B19 IgG was developed by infecting insect cells with recombinant baculovirus expressing the capsid protein VPI. The test was used to study the prevalence of antibodies in 725 healthy children and young adults living in Santiago, Chile. In total, 248 sera were taken in 1990 and 477 in 1996. The seroprevalence was low in children less than 5 years old (3% in 1990 and 21% in 1996). It rose during school age to a prevalence around 50%, reaching 60% in young adults. No differences were found between genders. There was a statistically significant higher seroprevalence in the low socioeconomic status group in 1990 samples, but this was not observed in 1996. The higher prevalence observed in children less than 5 years of age in 1996 compared with 1990 could be explained by the occurrence of intervening epidemics of parvovirus B19 infection.

Adolescent↗
PubMed2004

Seroprevalence of IgG against conformational and linear capsid antigens of parvovirus B19 in Italian blood donors.

Serum samples from 446 Italian blood donors between 18 and 65 years of age were analysed for the presence of IgG against parvovirus B19 capsid proteins VP1 and VP2 including conformational and linear epitopes. The overall prevalence of IgG against parvovirus B19 capsid proteins VP1 and VP2 against at least one antigen type was 79.1 %. No significant difference was found between men and women. In the 18-27 years age group, 77.0 % of the population had experienced infection with the virus, reaching 88.5 % in the 48-57 years age group. The overall prevalence of IgG was 78.0 % against conformational VP1 + VP2 antigens, 74.9 % against conformational VP2, 70.9 % against linear VP1 and 23.3 % against linear VP2 in the analysis of the IgG response against different conformational and linear epitopes of VP1 and VP2. Although IgG against conformational VP1+VP2, conformational VP2 and linear VP1 was present in more than 60 % of subjects in all age groups, IgG against VP2 linear antigens was present in only 32% of subjects in the 18-27 years age group and then decreased to 20.5 % in the 28-37 years age group. A different trend was noted when IgG positivity against linear and conformational epitopes was analysed separately in men and women. A significant increase was found in seroprevalence of IgG against VP2 conformational antigens with increasing age in males and a significant decrease in seroprevalence of IgG against VP2 linear antigens in women with increasing age.

Adolescent↗
PubMed2001

Novel cross-strand three-purine stack of the highly conserved 5'-GA/AAG-5' internal loop at the 3'-end termini of Parvovirus genomes.

We have used two-dimensional nuclear magnetic resonance (2D-NMR), distance geometry (DG) and molecular dynamics / energy minimization (MD/EM) methods to study a 2 x 3 asymmetric internal loop structure of the highly conserved 5'-(GA)/(AAG)-5' bubble' present at the 3'-end hairpin of the single-stranded DNA genome of parvoviruses. This motif contains an unpaired adenosine stacked between two bracketed sheared G.A pairs. However, the phenomenal cross-strand G-G and A-A stacking in the tandem sheared G.A pairs has undergone considerable change. A novel three-purine stacking pattern is observed instead; the inserted A18 base is completely un-stacked from its neighboring G 17 and A 19 bases, but well stacked with the cross-strand A4 and G3 bases to form a novel A4/A18/G3 stack that is different from the double G/G, A/A or quadruple G/G/G/G stack present in the 5'-(GA)/(AG)-5' or 5'-(GGA)/(AGG)-5' motifs. Unlike the bulged purine residue that usually causes about 20 degree kink in the helical axis of the parent helix when bracketed by canonical G.C or A.T base pairs, no significant kink is observed in the present helix containing a bulged-adenine that is bracketed by sheared G.A pairs. The phosphodiesters connecting G3-A4 and G17-A18 residues adopt unusual zeta torsional angles close to the trans domain, yet that connecting A18-A19 residues resumes the normal zeta(g-) value. The well structured '5'-(GAA)/(AG)-5" internal loop in the parvovirus genomes explains its resistance to single-strand specific endonuclease susceptibility.

Adenine↗
PubMed2002

Digital arterial occlusive disease and parvovirus B19 infection.

We report a case of a 37-year-old white woman, who presented with digital arterial occlusions associated with parvovirus B19 infection. Two other member of the family presented acute febrile illness, polyarthralgia (husband), and erythema infectiosum (son) during the same month. This new report gives weight to the concept that acute human parvovirus infection could become part of the differential diagnosis of acute digital occlusive arteriopathy.

Adult↗
PubMed2006

Increasing the capacity of parvovirus-retentive membranes: performance of the Viresolve Prefilter.

Removal of small parvoviruses from highly purified proteins can be performed using normal-flow filters. The entrapment of protein aggregates, denatured proteins and other impurities can cause plugging and a decrease in filter capacity. In the present study a variety of prefilters were investigated for their ability to remove the species that foul Viresolvetrade mark NFP (normal-flow parvovirus) filters. The Viresolvetrade mark Prefilter, which utilizes entrapped diatomaceous earth to hydrophobically bind fouling species, provided a dramatic increase in virus filter capacity for solutions containing human IgG or a variety of monoclonal antibodies. We found that the component of the human IgG stream that bound to the Prefilter, when analysed using SDS/PAGE, isoelectric-focusing, size-exclusion chromatography, CD and ANS (1-anilinonaphthalene-8-sulphonate) titration, consisted of monomeric IgG variants containing more exposed hydrophobic surfaces. The bound component may represent oxidized or otherwise degraded IgG species or a subset of IgG molecules with more hydrophobic antigen-binding surfaces. The results indicate that NFP membranes do not foul solely as a result of entrapment of protein aggregates in the pore structure. The Viresolvetrade mark Prefilter has a high permeability, did not diminish protein yield and provided consistent performance between different media lots, device lots and device scales.

Adsorption↗