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Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins.

Infections caused by human parvovirus B19 are known to be controlled mainly by neutralizing antibodies. To analyze the immune reaction against parvovirus B19 proteins, four cell lines secreting human immunoglobulin G monoclonal antibodies (MAbs) were generated from two healthy donors and one human immunodeficiency virus type 1-seropositive individual with high serum titers against parvovirus. One MAb is specific for nonstructural protein NS1 (MAb 1424), two MAbs are specific for the unique region of minor capsid protein VP1 (MAbs 1418-1 and 1418-16), and one MAb is directed to major capsid protein VP2 (MAb 860-55D). Two MAbs, 1418-1 and 1418-16, which were generated from the same individual have identity in the cDNA sequences encoding the variable domains, with the exception of four base pairs resulting in only one amino acid change in the light chain. The NS1- and VP1-specific MAbs interact with linear epitopes, whereas the recognized epitope in VP2 is conformational. The MAbs specific for the structural proteins display strong virus-neutralizing activity. The VP1- and VP2-specific MAbs have the capacity to neutralize 50% of infectious parvovirus B19 in vitro at 0.08 and 0.73 microgram/ml, respectively, demonstrating the importance of such antibodies in the clearance of B19 viremia. The NS1-specific MAb mediated weak neutralizing activity and required 47.7 micrograms/ml for 50% neutralization. The human MAbs with potent neutralizing activity could be used for immunotherapy of chronically B19 virus-infected individuals and acutely infected pregnant women. Furthermore, the knowledge gained regarding epitopes which induce strongly neutralizing antibodies may be important for vaccine development.

Amino Acid Sequence↗

Clinical interpretation of antineutrophil cytoplasmic antibodies: parvovirus B19 infection as a pitfall.

BACKGROUND: While antibodies directed against proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA) have a high specificity for the diagnosis of systemic vasculitis, they may also be found as an epiphenomenon of acute viral infection. OBJECTIVE: To investigate whether positive ANCA test results may be a common feature of acute parvovirus B19 infection. METHODS: Sera were analysed from 1242 patients from a rheumatology outpatient clinic for reactivity with parvovirus B19 and EBV antibodies. They were tested for the presence of PR3-ANCA and MPO-ANCA, along with sera known to contain IgM antibodies to these viruses obtained from among 41,366 samples submitted for virological screening. RESULTS: ANCA were found in 10% (5/50) of the sera positive for IgM antibodies to parvovirus and in 3/51 sera containing IgM antibodies to EBV. Three of six patients with arthritis and concomitant parvovirus infection were found positive for PR3-ANCA and two were found positive for MPO-ANCA. All six patients tested negative for ANCA after six months of follow up. CONCLUSIONS: PR3-ANCA and MPO-ANCA may occur transiently in patients with acute B19 infection or infectious mononucleosis, highlighting the importance of repeated antibody tests in oligosymptomatic clinical conditions in which systemic autoimmune disease is suspected.

Acute Disease↗

Congenital parvovirus B19 infection: experience of a recent epidemic.

OBJECTIVE: We report the management and outcome of 6 cases of non-immune fetal hydrops secondary to parvovirus B19 infection presenting over a 5-month period. METHODS: The Queen Mothers Hospital is a tertiary referral centre for fetal medicine. All cases were suspected on the basis of ultrasound evidence of hydrops. Two cases were managed conservatively owing to the presence of an active fetus with evidence of resolving hydrops. Fetal blood sampling intra-uterine transfusion and drainage of ascitic fluid were performed in 3 cases. The 6th case unfortunately resulted in an intra-uterine death prior to fetal blood sampling. RESULTS: Maternal parvovirus specific B19 was identified in all cases. Fetal parvovirus B19 IgM was identified in the 3 cases in whom fetal blood sampling was performed. A single intra-uterine transfusion was performed in these 3 cases; fetal hydrops resolved in 2 of these pregnancies progressing to the birth of a healthy baby at term, whereas 1 case was complicated by intra-uterine death. Fetal hydrops resolved in both cases managed conservatively, leading to the birth of a healthy baby at term. CONCLUSIONS: Parvovirus B19 infection should always be suspected in cases of non-immune hydrops. Conservative management will be appropriate in some cases and should involve weekly ultrasonography. The outlook for pregnancies presenting with gross hydrops remains guarded, even if intra-uterine transfusion is performed successfully.

Adult↗

Detection of rat parvovirus type 1 and rat minute virus type 1 by polymerase chain reaction.

Two newly recognized parvovirus species, rat parvovirus 1 (RPV-1) and rat minute virus 1 (RMV-1), were recently identified in naturally infected rats. In this study, two polymerase chain reaction (PCR) assays were developed to specifically detect RPV-1 and RMV-1. The RPV-1 PCR assay amplified the expected 487-bp deoxyribonucleic acid (DNA) fragment only in the presence of RPV-1 DNA; the RMV-1 PCR assay amplified the expected 843-bp product only from RMV-1 DNA, not from other rodent parvoviruses. The RPV-1 and the RMV-1 PCR assays detected approximately 18 and 70 copies of DNA template, respectively. These two PCR assays were shown to be sensitive, specific and rapid methods for detecting RPV-1 and RMV-1 infections in rats. These assays may also be valuable for evaluation of biological specimens for parvovirus contamination.

Animals↗

Immune-mediated inner ear disease and parvovirus B19.

Human parvovirus B19 (HP-B19), the etiologic agent of the common childhood illness erythema infectiosum, has been implicated in systemic immune disorders. Patients presenting with sensorineural hearing loss and/or dizziness, not readily categorized, were evaluated for immune-mediated inner ear disease. Appropriate serologic studies including parvovirus B19 antibody titers were conducted. Thirty patients with suspected immune-mediated inner ear disease were treated with corticosteroid trial for 5 to 7 days, then reexamined with repeat audiogram and/or vestibular testing. Seventeen patients with clinical response were treated with long-term corticosteroids and cyclophosphamide. Six patients had positive HP-B19 immunoglobulin M (IgM) titers and 8 patients had positive parvovirus immunoglobulin G (IgG) titers. All 14 patients responded to therapy. Parvovirus B19, therefore, is a possible etiology of immune-mediated inner ear disease.

Adrenal Cortex Hormones↗

Systemic lupus erythematosus and parvovirus B-19: casual coincidence or causative culprit?

Systemic lupus erythmatosus (SLE) is a multi-system autoimmune disease characterized by auto-reactive cells and auto-antibodies, which can potentially affect all organ systems. Typical organ systems that are affected include the heart, lungs, skin, kidneys, and central nervous system. Its expression is believed to be dependent on various factors such as genetic predisposition, environmental agents, immune dysregulation, crossreactivity with auto-antigens, alterations in auto-antigens, or most likely, a combination of these. Parvovirus B19, a virus which commonly runs an asymptomatic or benign self-limiting course such as erythema infectiosum, transient aplastic crisis, flu-like symptoms, rash, arthalgia, and arthritis, has recently been associated with a number of rheumatic diseases, more specifically with SLE. Like SLE, it can present with multi- systemic symptoms resembling SLE both clinically and serologically. Similarities have been so striking that patients have been initially misdiagnosed with SLE, having fulfilled 3-5 of the criteria of the American College of Rheumatology, currently used for the diagnosis of SLE, only to discover later that they were infected by parvovirus B19. This paper will discuss parvovirus' link to SLE, its similarities and differences, and whether parvovirus can act as a trigger of, or simply mimic, SLE.

Diagnosis, Differential↗

Detection of parvovirus B19, cytomegalovirus and enterovirus infections in cases of intrauterine fetal death.

AIMS: Maternal infections with parvovirus B19, cytomegalovirus (CMV) and enterovirus have been associated with intrauterine fetal death (IUFD), but the incidence of these infections is not clear. This prospective study was conducted to estimate this incidence. METHODS: A prospective study of 38 months was conducted on cases of IUFD referred to Huddinge University Hospital, Stockholm, Sweden. Placental biopsies, fetal blood and amniotic fluid were collected from cases of IUFD (n=52). Placental biopsies from normal pregnancies at term (n=53) were used as controls. These tissues were examined for parvovirus B19 DNA, CMV DNA and enterovirus RNA using polymerase chain reaction (PCR). Maternal viral serology was measured in 46 cases and virus isolation for enterovirus in maternal stool samples was performed in 31 cases. RESULTS: Viral nucleic acid was recovered in at least one tissue sample from six cases of fetal death (parvovirus B19 in two cases, CMV in three and enterovirus in one), while all placental biopsies from controls were found negative. Serological signs of primary maternal infection were found in two of the cases, and virus isolation for enterovirus was negative in all samples examined. CONCLUSION: Parvovirus B19, CMV and enterovirus may be considered as etiologic agents in cases of fetal death. PCR on placental and/or fetal tissue improves diagnostic accuracy for these infections.

Adult↗

Parvovirus vectors for cancer gene therapy.

Parvoviruses comprise a group of single-stranded DNA viruses with greater potential for gene therapy applications. Unique characteristics of paroviruses, such as non-pathogenicity, antioncogenicity and methods of efficient recombinant vector production, have drawn more attention towards utilising parvovirus-based vectors in cancer gene therapy. Although > 30 different parvoviruses have been identified so far, recombinant vectors derived from adeno-associated virus (AAV), minute virus of mice (MVM), LuIII and parvovirus H1 have been successfully tested in many preclinical models of human diseases, including cancer. The present article will focus on the potential of non-replicating and autonomously replicating parvoviral vectors in cancer gene therapy, including strategies that target tumour cells directly or indirectly.

Animals↗

Development of ELISA using recombinant antigens for specific detection of mouse parvovirus infection.

Nucleotide sequences of mouse parvovirus (MPV) isolate, named MPV/UT, and mouse minute virus (MMV) were analyzed and used for expressing recombinant proteins in E. coli. ELISA tests using recombinant major capsid protein (rVP2) and recombinant major non-structural protein (rNS1) as antigens were developed and their performance in serologic detection of rodent parvovirus infection was assessed. MPV-rVP2 and MMV-rVP2 ELISAs reacted specifically with anti-MPV and anti-MMV mouse sera, respectively. MMV-rNS1 antigen had a wide reaction range with antisera to rodent parvoviruses including MPV, MMV, Kilham rat virus (KRV) and H-1 virus. All mice oronasally infected with MPV were seropositive at 4 weeks post-infection in screening by ELISAs using MPV-rVP2 and MMV-rNS1 antigens, but were negative by conventional ELISA using whole MMV antigen. A contact transmission experiment revealed that transmission of MPV occurred up to 4 weeks post-infection, and all cage mates were seropositive in screening with MPV-rVP2 and MMV-rNS1 ELISAs. These results indicate that MPV-rVP2 and MMV-rVP2 are specific ELISA antigens which distinguish between MPV and MVM infection, while MMV-rNS1 antigen can be used in generic ELISA for a variety of rodent parvoviruses. The higher sensitivity of MPV-rVP2 ELISA than conventional ELISA for detecting seroconversion to MPV in oronasally infected mice as well as in cage mates suggests the usefulness of MPV-rVP2 ELISA in quarantine and microbiological monitoring of MPV infection in laboratory mice.

Animals↗

Clinical manifestations and outcomes of parvovirus B19 infection during pregnancy in Japan.

Parvovirus B19 is a small DNA virus. Infection with parvovirus B19 during pregnancy may cause serious complications in the fetus, including hydrops fetalis and fetal death. The purpose of the present study is to clarify the clinical manifestations and outcomes of parvovirus B19 infection during pregnancy. This prospective study enrolled 478 women with suspected B19 infections during pregnancy between 1999 and 2004. One hundred cases (21%) of B19 infection were detected in 478 pregnant women who had been exposed to B19. Serological infection was confirmed by measurement of B19-specific IgM and IgG in sera. Forty-nine cases reported maternal clinical symptoms and 51 cases were asymptomatic. Facial rash was the most common symptom, with 51% (25/49) of the symptomatic patients complaining of either a facial, body or limb rash. The most common infectious source was children living in the home. Overall, the incidence of adverse fetal effects (including hydrops fetalis and fetal death) related to intrauterine B19 infection was 7% (7/100), and all seven cases were exposed to B19 infection before 20 weeks of gestation. Although half of the cases with parvovirus B19 infections during pregnancy were asymptomatic, patients with adverse fetal effects tended to be symptomatic including rash and fever. These clinical data may supply useful information to produce clinical guidelines for managing B19 infection during pregnancy.

Abortion, Spontaneous↗

Serologic response of maned wolves (Chrysocyon brachyurus) to canine and canine parvovirus vaccination distemper virus.

This study evaluated the immune response of 47 (22 males, 25 females) captive maned wolves (Chrysocyon brachyurus) to modified-live canine parvovirus and canine distemper virus (Onderstepoort and Rockborn strains) vaccines. Sera were collected from 33 adults and 14 pups, including five free-ranging pups captured at 1 yr of age or younger. All the adults and four captive-born pups had been vaccinated prior to this first blood collection. Virus neutralization and hemagglutination-inhibition assays were performed for quantitating antibodies against canine distemper and canine parvovirus, respectively. Distemper antibody titers > or = 100 were present in 57% of adults and 14% of pups. All adults and 29% of pups had parvovirus antibody titers > or = 80. After vaccination, 72% of the wolves developed antibody titers > or = 100 against distemper and 98% developed titers > or = 80 against parvovirus. Both vaccines used were safe and immunogenic to juvenile and adult maned wolves, regardless of prior vaccination history.

Animals↗

Prevalence of antibodies against parvovirus B19 in Norwegians with congenital coagulation factor defects treated with plasma products from small donor pools.

The seroprevalence of antibodies against parvovirus B19 in 308 Norwegians with coagulation factor defects of different types and severities was assessed by an IgG antibody capture radioimmunoassay (GACRIA). The overall seroprevalence was 62%. The seroprevalence among subjects with different types of coagulation factor defects was related to the type and severity of the coagulation factor defect: severe hemophilia A 64%, moderate and mild hemophilia A 58%, severe hemophilia B 88%, moderate and mild hemophilia B 73%, and von Willebrand's disease 52%. The prevalence of parvovirus B19 antibodies among household contacts and blood donors was 49% and 42% respectively. This study confirms that replacement therapy with coagulation factors is accompanied by an increased risk for acquiring parvovirus B19 infection. However, the prevalence of parvovirus B19 antibodies among Norwegian hemophiliacs is well below the prevalence reported from other countries and probably reflects the small numbers of donors in plasma pools used for the preparation of coagulation factor concentrates.

Adult↗

Fulminant parvovirus infection following erythropoietin treatment in a patient with acquired immunodeficiency syndrome.

We report the case of a 41-year-old black man with acquired immunodeficiency syndrome who developed a severe chronic anemia due to parvovirus infection. Bone marrow biopsy revealed erythroid aplasia. The infectious nature of the anemia was not recognized, and the patient was treated with erythropoietin. The patient's reticulocyte response was inadequate, however, and he remained anemic. A second bone marrow biopsy showed erythroid hyperplasia and prominent intranuclear parvovirus inclusions within erythroid progenitors. Erythropoietin was discontinued and was followed by a course of intravenous immunoglobulin, which resulted in rapid correction of anemia. To our knowledge, this is the first reported case of fulminant human parvovirus infection exacerbated by erythropoietin administration and documented by sequential bone marrow histologic examination. This case illustrates the critical importance of considering parvovirus in the etiology of chronic anemia with erythroid aplasia in immunocompromised patients.

AIDS-Related Opportunistic Infections↗

Parvovirus infections in wild carnivores.

Various parvoviruses infect carnivores and can cause disease. In this review article the knowledge about infections of free-ranging or captive carnivores with the feline parvoviruses, feline panleukopenia virus, and canine parvovirus, including the antigenic types CPV-2a and -2b, as well as Aleutian disease of mink virus and minute virus of canines are summarized. Particular emphasis is placed on description of the evolution of canine parvovirus which apparently involved wild carnivore hosts.

Animals↗

Humoral immunity and protection of mice challenged with homotypic or heterotypic parvovirus.

BACKGROUND AND OBJECTIVES: Two serotypes of autonomously replicating parvoviruses infect laboratory mice. Genome regions coding for the nonstructural proteins of minute virus of mice [MVM] and mouse parvovirus [MPV] are almost identical, whereas capsid-coding sequences are divergent. We addressed these questions: Does humoral immunity confer protection from acute infection after challenge with homotypic or heterotypic parvovirus, and if it confers protection against acute MPV infection, does it also protect against persistent MPV infection? METHODS: Infant mice without maternal antibody or antibody to MVM or MPV and young adult mice given normal mouse serum or antibody to MVM or MPV were challenged with homotypic or heterotypic virus. In situ hybridization with target tissues was the indicator of infection. RESULTS: Humoral immunity failed to confer protection against acute heterotypic parvovirus infection. In passive transfer studies, MPV DNA was observed occasionally in lymph nodes, intestine, or the spleen of MPV-challenged mice given homotypic antibody and kept for 6 or 28 days. Variable proportions of mice given MPV antibody and homotypic challenge had viral DNA in lymphoid tissues 56 days after virus inoculation. CONCLUSION: A mouse or colony that has sustained infection with MVM or MPV is probably fully susceptible to infection with the heterotypic virus.

Animals↗

[Parvovirus B19 as a cause of acute arthritis].

Parvovirus B19 is known to cause erythema infection (fifth disease), acute and chronic arthritis, aplastic crises in chronic hemolytic anemia, chronic anemia in the immunocompromised host and hydrops fetalis. We present two patients with acute arthritis due to parvovirus infection. Both had symmetrical synovitis in wrists and ankles. Patient 1 presented with fever and rash before joint symptoms occurred; patient 2 had joint symptoms only. Arthritis due to parvovirus is usually self-limited, but may develop into a chronic disease similar to rheumatoid arthritis. Parvovirus should be considered one of the differential diagnoses while dealing with acute or chronic arthritis.

Acute Disease↗

Detection of a human parvovirus intrauterine infection with the polymerase chain reaction.

OBJECTIVE: To detect human parvovirus B19 intrauterine infection in pregnancy with the polymerase chain reaction (PCR). STUDY DESIGN: DNA of chorionic villi and amniotic fluid was extracted and the gene of human parvovirus B19 amplified with PCR. RESULTS: The study analyzed 61 specimens of chorionic villi and 26 specimens of amniotic fluid and found two positive specimens of chorionic villi and 1 positive specimen of amniotic fluid. CONCLUSION: The vertical transmission of human parvovirus B19 infection in early pregnancy may be a pathway of intrauterine infection. Chorionic villus sampling in early pregnancy and PCR could be developed as a method of prenatal diagnosis of human parvovirus B19 intrauterine infection.

Adult↗

[Leukocytopenia and thrombocytopenia preceded by human parvovirus B19 infection: report of three adult cases].

In Saiki City, Oita, Japan, erythema infectiosum in children has been prevalent from June, 1999 to the time of writing (January, 2000). We present three adult cases of parvovirus B19-associated leukocytopenia and thrombocytopenia that developed during this epidemic. Between June and November, 1999, a 32-year-old woman, a 38-year-old woman, and a 63-year-old man were referred to our hospital for treatment of leukocytopenia and thrombocytopenia. All complained of common cold-like symptoms. Their WBC counts (percentage of neutrophils) were 1,000/microliter (70%), 1,900/microliter (40%) and 1,680/microliter (40%), their hemoglobin levels 9.4 g/dl, 9.8 g/dl and 14.9 g/dl, and their platelet counts 10.8 x 10(4)/microliter, 6.9 x 10(4)/microliter and 4.5 x 10(4)/microliter, respectively. The diagnosis of parvovirus B19 infection was documented by the presence of B19-specific IgM antibodies or serum positivity for viral DNA. In two cases, the leukocytopenia and thrombocytopenia resolved gradually. In the other case, leukocytopenia, thrombocytopenia and B19 infection persisted for more than two months. These cases suggest that parvovirus B19 may be a common cause of leukocytopenia and thrombocytopenia even in adult patients without hematological disorders (erythropoietic stress), and that testing for parvovirus infection is justified in such patients, even if anemia is slight, especially when erythema infectiosum is prevalent.

Adult↗