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Parvovirus B19 infection in a twin pregnancy.

BACKGROUND: Parvovirus infection has been associated with the development of nonimmune hydrops fetalis in pregnancy. This report describes a twin pregnancy in which one fetus was affected by parvovirus B19 and the other was not. CASE: A 35-year-old woman was found to have a twin gestation at genetic amniocentesis. Subsequent ultrasound at 18 weeks showed that twin B had evidence of hydrops fetalis. Serum from the mother tested positive for parvovirus B19 immunoglobulin (Ig) G and IgM. Cultured amniotic fluid from twin B was subsequently found to be positive for parvovirus B19. At 20 weeks' gestation, the hydropic fetus died. The unaffected fetus grew normally. At 40 weeks, the unaffected fetus was delivered vaginally with no difficulties. Cord blood from the unaffected fetus was negative for parvovirus B19 IgM. CONCLUSION: This case demonstrates differential infection of parvovirus B19 in a diamniotic, dichorionic twin pregnancy. One twin developed signs of hydrops fetalis consistent with parvovirus B19. The diagnosis was confirmed immunologically and by amniotic fluid culture. The second twin had no evidence of parvovirus B19 and no immunologic suggestion of infection at birth. This is the only known report of such differential transmission of parvovirus B19 in a twin pregnancy.

Adult↗

Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection.

OBJECTIVE: To show a possible association between parvovirus B19 infection and the presence of antiphospholipid antibodies (aPL) in patients with rheumatic diseases. METHODS: Serum samples obtained from 88 children with various forms of juvenile rheumatic disease and from 40 adults with systemic lupus erythematosus, the antiphospholipid syndrome, or other rheumatic disease, who had previously been tested and shown to be positive for IgG aPL, were analyzed for the presence of B19 DNA, for antibodies against the B19 viral proteins VP1, VP2, and NS1, and for IgG aPL (anticardiolipin, anti-beta(2)-glycoprotein I, and antiphosphatidylserine). As controls, serum samples obtained from 135 children with noninflammatory bone diseases or growth retardation were also analyzed. RESULTS: Twenty-four (27%) of the 88 children with rheumatic diseases had detectable amounts of IgG aPL. Fourteen (58%) of these 24 IgG aPL-positive patients showed IgG against VP1/VP2 and viral genomes, indicating the presence of acute (2 patients) or persistent (12 patients) infection. Past parvovirus B19 infection was identified in 7 (29%) of 24 IgG aPL-positive children, as indicated by VP1/VP2-specific IgG in the absence of viral DNA. Three (12%) of 24 IgG aPL-positive children had not been infected with B19. Sixty-nine (51%) of 135 control children displayed VP1/VP2-specific IgG. Three (2%) of these 135 children were IgG aPL positive (2 children had past parvovirus B19 infection, and 1 was negative for parvovirus B19). Analysis of the parvovirus B19 status of 40 adult IgG aPL-positive patients showed that 33 (83%) were anti-IgG VP1/VP2-positive, and viral DNA was detected in 11 patients (28%). Ten of these 11 viremic patients were in the subgroup of 28 IgG aPL-positive SLE patients. CONCLUSION: Antiphospholipid antibodies are preferentially found in serum of children with juvenile idiopathic arthritis who have been previously infected with parvovirus B19 and have established, persistent infection. Adult patients with IgG aPL positivity have a high incidence of persistent parvovirus B19 infection. We conclude that parvovirus B19 might be directly involved in the elicitation of autoimmune reactions partly mediated by aPL.

Acute Disease↗

Vectors based on autonomous parvoviruses: novel tools to treat cancer?

Autonomous parvoviruses are small nuclear-replicating DNA viruses. The rodent parvoviruses usually are non- or weakly pathogenic in adult animals, bind to surface receptors which are expressed on most cells, and do not appear to integrate into host chromosomes during either lytic or persistent infections. Interestingly, malignant transformation of the target cells was often found to correlate with an increase in their capacity for amplifying and/or expressing the incoming parvoviral DNA, and is associated with oncolysis, i.e., the selective killing of the infected tumor cells. Moreover, the closely related parvoviruses MVM, H-1 and LuIII efficiently infect human cell lines. This finding makes these parvoviruses promising candidate vectors for therapies that require transient expression of a transduced gene. In particular, parvoviruses may be suitable to target and kill tumor cells and simultaneously deliver appropriate transgenes, e.g., genes coding for immuno-stimulatory factors. Pilot experiments performed in animals to assess whether parvovirus-based vectors carrying the interleukin 2 (IL-2) cytokine gene have reinforced anti-cancer capacity showed that these recombinant viruses suppressed tumor formation more efficiently than viruses devoid of a transgene. Strong anti-cancer effects of recombinant parvoviruses expressing interferon gamma-inducible protein 10 (IP-10) and monocyte chemotactic protein 3 (MCP-3) were also observed against established hemangiosarcomas and melanomas in immuno-competent mice, respectively. Altogether, these data illustrate the enormous potential of recombinant autonomous parvoviruses as anti-tumor agents and give hope of using them against human cancer.

Animals↗

Recurrent high level parvovirus B19/genotype 2 viremia in a renal transplant recipient analyzed by real-time PCR for simultaneous detection of genotypes 1 to 3.

Organ transplant recipients infected with parvovirus B19 frequently develop persistent viremia associated with chronic anemia and pure red cell aplasia. In this study, a male renal transplant recipient who had been infected with parvovirus B19/genotype 2 after renal transplantation at the age of 34 years is described. The patient was repeatedly treated with high dose intravenous immunoglobulin (IVIG) that resulted in the resolvement of symptoms but not in virus eradication. During an observation period of 33 months after transplantation three phases associated with high parvovirus B19 viremia were observed. Both the first and the second viremic phases were combined with severe anemia. Parvovirus B19 specific IgM-antibodies were initially detected at the beginning of the second phase in continually rising concentrations. Initially eradication of the virus by immunoglobulin therapy was reported after the first viremic phase [Liefeldt et al. (2002): Nephrol Dial Transplant 17:1840-1842]. Retrospectively this statement has to be corrected. It was based on the use of a qualitative PCR assay specific for parvovirus B19 genotype 1 associated with reduced sensitivity for detection of genotype 2. After sequence analysis of the viral DNA and adjustment of a real-time PCR assay (TaqMan) for quantitative detection of all three B19 virus genotypes analysis of consecutive serum samples allowed the demonstration of long lasting phases with reduced viral loads following IVIG-treatment. These results demonstrate that IVIG treatment of parvovirus B19-triggered anemia in transplant recipients offers an opportunity to resolve symptoms, but does not guarantee eradication of the virus. Since reactivation of parvovirus B19 infection can result in high virus load associated with the recurrence of symptoms repeated screening for viral DNA is recommended using the TaqMan system established for quantitative detection of all three genotypes of parvovirus B19.

Adult↗

Is parvovirus B19 the cause for autoimmunity against the angiotensin II type receptor?

Initial studies have demonstrated the significance of the agonistic angiotensin II receptor AT1 autoantibody (AT1-AA) in preeclampsia, although it is unclear what factors induce its generation. Since the epitope recognized by AT1-AA shares high homology with parvovirus B19 (PVB19) capsid proteins, we have investigated the relationship between the presence of AT1-AA in maternal circulation and PVB19 sero-prevalence in normal and abnormal pregnancy. We determined the parvovirus IgG sero-prevalence in normal pregnancies in the second trimester and those with abnormal uterine perfusion that are at risk for preeclampsia. Secondly, pregnancies at delivery with preeclampsia or intrauterine growth restriction were included. All women with normal perfusion were AT1-AA-negative and 80% were parvovirus-IgG-positive. Sixty-three percent of pregnancies with abnormal uterine perfusion were AT1-AA-positive and 71% IgG-positive. Fifty-two percent of the IgG-positive pregnancies in this subgroup were also AT1-AA-positive, and 9 of the 10 parvovirus IgG-negative women were AT1-AA-positive. In the third trimester, 87% of pregnancies with manifest disease were AT1-AA-positive and 58% IgG-positive. While 79% of the PVB19 IgG-positive pregnancies were also AT1-AA-positive, all parvovirus IgG-negative women were AT1-AA-positive. In all groups, AT1-AA activity did not differ between parvovirus IgG-negative and positive women. We find parvovirus IgG-positive pregnant women in all subgroups without relation to AT1-AA presence. This favors AT1-AA generation to be independent of epitope mimicry between parvovirus B19 capsid proteins and the AT1 receptor.

Animals↗

TaqMan real-time PCR for detection of hepatopancreatic parvovirus from Australia.

Hepatopancreatic parvovirus is an emerging disease in crustacean aquaculture. Consequently, methods of detection are needed that enable the sensitive detection and confirmation of the virus better than currently used methods such as histology and conventional polymerase chain reaction (PCR). A TaqMan based real-time PCR assay was developed for the detection of the Australian isolate of hepatopancreatic parvovirus which is only 85% similar to its nearest known relative. The TaqMan assay was developed within the capsid protein region of the genome and is optimised to detect as little as 10 copies of the targeted sequence per PCR vial. The hepatopancreatic parvovirus primers and probe were HPV140F 5'-CTA CTC CAA TGG AAA CTT CTG AGC-3', HPV140R 5'-GTG GCG TTG GAA GGC ACT TC-3' and HPV140probe 5'-FAM TAC CGC CGC ACC GCA GCA GC TAMRA-3', respectively. The assay was specific for the hepatopancreatic parvovirus strain from Australian Penaeus merguiensis as it did not detect related crustacean and canine parvoviruses from Australia. In addition, the very low homology of the target sequence with published sequences from the Thai and Korean strains of hepatopancreatic parvovirus and other prawn viruses such as WSSV, suggested this assay would be specific for the Australian hepatopancreatic parvovirus isolate. Furthermore, it detected hepatopancreatic parvovirus in 22/22 wild-caught P. merguiensis clinical samples and 473/545 (87%) farmed P. merguiensis. This assay has the potential to be used for diagnostic purposes and in robotic applications, particularly for the detection and quantitation of low-grade infections.

Animals↗

Human parvovirus B19 in bone marrows from adults with acquired immunodeficiency syndrome: a comparative study using in situ hybridization and immunohistochemistry.

Human parvovirus B19, which infects and lyses erythroid precursors, can cause severe anemia in patients with immunodeficiency. The incidence of parvovirus infection in adult acquired immunodeficiency syndrome (AIDS) patients is unknown. Eighty-one archival formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies from 73 AIDS adults were immunostained with monoclonal R92F6 against B19 VP1 and VP2 capsid proteins using streptavidin peroxidase and streptavidin alkaline phosphatase techniques. In addition, the same tissues were hybridized in situ with a digoxigenin-labeled parvovirus B19 DNA probe. Five FFPE bone marrows, from 3 HIV-negative patients with positive immunoglobulin M (IgM) serology for parvovirus B19, and 1 parvovirus B19-infected fetal liver were positive controls. By immunoperoxidase, all tissues were negative with R92F6 except the fetal liver, which exhibited strong positivity predominantly in viral inclusions. With immunoalkaline phosphatase, all positive controls were immunoreactive with R92F6; however, the AIDS marrows were negative. With in situ hybridization (ISH), all positive controls and 7 of 81 (8.6%) of AIDS marrows were positive for B19 parvovirus DNA. We conclude that ISH is more sensitive than R92F6 immunohistochemistry in parvovirus B19 detection. A small but significant number of bone marrows from AIDS adults shows evidence of human parvovirus B19 infection.

Acquired Immunodeficiency Syndrome↗

Parvovirus B19 viraemia in Dutch blood donors.

Blood, donated by asymptomatic donors, may contain and transmit parvovirus B19. To investigate the dynamics of parvovirus viraemia in asymptomatic blood donors, we studied the amounts of parvovirus DNA in pools of donor plasma, the prevalence of parvovirus antibodies among blood donors in relation to age, and the seasonal and year-to-year variation of the incidence of parvovirus infection in The Netherlands. The incidence of parvovirus infection follows a seasonal cycle and a cycle of several years. Among Dutch blood donors the incidence was estimated to be 0.56% per year. Forty seven out of 100 pools of 5000 plasma donations tested positive for parvovirus DNA. We inferred that the course of viraemia in asymptomatic donors shows a short peak (> 10(9) copies parvovirus DNA/ml), followed by viraemia below 10(6) copies/ml for about 2 weeks.

Adolescent↗

Prevalence of parvovirus B19 infection in patients infected with human immunodeficiency virus.

Parvovirus B19 infection may cause chronic anemia in human immunodeficiency virus (HIV)-infected hosts. Small-scale studies and case reports have suggested that parvovirus B19 infection is a significant cause of anemia in HIV-infected patients. We studied single serum samples from 317 consecutive HIV-infected patients with use of parvovirus B19-specific serology and polymerase chain reaction for detection of viral DNA. Anemia was noted in 176 patients (55.5%); 126 (39.9%) had < 0.10 x 10(9) CD4+ cells/L. In this study group, 191 (60.3%) of the patients were positive for parvovirus B19 IgG. Seroprevalence rates did not differ between patients with low and higher CD4+ cell counts or between anemic and nonanemic patients. Parvovirus B19 DNA was detected in none of the sera. In a control group of 226 healthy male blood donors, the seroprevalence of parvovirus B19 IgG was 68.1%; two IgG-positive sera also contained parvovirus B19 DNA. This study demonstrates that chronic parvovirus B19 infection should not be considered a frequent cause of anemia in HIV-infected individuals.

AIDS-Related Opportunistic Infections↗

Parvovirus B19 infection as a cause of anemia in pediatric acute lymphoblastic leukemia patients during maintenance chemotherapy.

PURPOSE: Persistent parvovirus B19 tends to occur in immunocom-promised patients and manifests as pure red cell aplasia and chronic anemia. This study aimed to detect the contribution of parvovirus B19 infection to anemia in children with acute lymphoblastic leukemia (ALL) receiving chemotherapy. PATIENTS AND METHODS: Two groups of ALL patients were studied during maintenance chemotherapy: 50 patients with persistent anemia (ie, extending for >2 weeks) and 34 patients without anemia (controls). Serum parvovirus B19 IgG and IgM were investigated by an enzyme-linked immunosorbent assay, and the virus DNA was sought in bone marrow cells by a nested polymerase chain reaction assay. RESULTS: Parvovirus B19 DNA was detected in 11 of the 50 (22%) ALL children with anemia, 4 of whom were also IgM positive. In addition, IgM positivity was observed in nine (18%) other children who were negative for parvovirus B19 DNA. The children without anemia were found to be significantly different than those with anemia in terms of parvovirus B19 DNA positivity and DNA + IgM positivity (P = 0.03 and 0.01, respectively). IgG was found to be positive in a total of 19 (38%) cases, with B19 DNA present in 6 of them. CONCLUSIONS: These findings indicate the high frequency of parvovirus B19 in anemia in children with ALL and the importance of testing for its DNA in the bone marrow cells together with IgG and IgM antibodies in the serum of immunocompromised patients. It is important to consider parvovirus B19 infections as a cause of anemia and suppressed erythropoiesis in children with ALL who are receiving ongoing treatment.

Anemia↗

Increased prevalence of human parvovirus B19 DNA in systemic sclerosis skin.

BACKGROUND: Human parvovirus B19 is a small, single-stranded DNA virus encoding two structural capsid proteins and a nonstructural protein. It is the aetiological agent of erythema infectiosum and transient aplastic crisis in patients with haemolytic anaemia, and has been associated with fetal death, arthritis and chronic anaemia. In recent years, the possible involvement of parvovirus B19 in systemic sclerosis (SSc) has been reported. OBJECTIVES: To determine whether human parvovirus B19 DNA can be detected in SSc skin tissue specimens. METHODS: Normal subjects (n = 97) and patients with SSc (n = 48), systemic lupus erythematosus (n = 16), dermatomyositis (n = 8), morphoea (n = 6) and graft-versus-host disease (n = 8) were studied. Crude DNA was extracted from skin tissue specimens. We attempted to determine whether human parvovirus B19 could be detected in the skin of SSc using nested polymerase chain reaction (PCR). PCR amplification was performed with specifically designed first and second primer pairs for parvovirus B19 DNA. RESULTS: After the first PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated in comparison with that in normal controls (50 of 97, 52%) (P < 0.01). After the second PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated compared with that in normal controls (53 of 97, 55%) (P < 0.02). The occurrence rates in the other diseases showed no significant difference from that in normal controls. CONCLUSIONS: The increased prevalence of human parvovirus B19 DNA in SSc skin showed the possibility that the virus may be involved in the formation of skin tissue abnormalities in the disease.

Adult↗

Detection of newly recognized rodent parvoviruses by PCR.

Several autonomous parvovirus isolates distinct from the prototypic rodent parvoviruses have recently been identified. These include variants of a mouse orphan parvovirus (MOPV) and a hamster isolate designated hamster orphan parvovirus (HOPV). In this study, a PCR primer set specific for these newly identified rodent parvoviruses was designed on the basis of DNA sequence comparisons of these isolates with other autonomous parvoviruses. The specificity of the primer set was determined by testing viral preparations of seven different parvoviruses and eight other viruses known to infect rodents. The PCR assay amplified the expected 260-bp product only in the presence of DNA from MOPV, HOPV, or LuIII a parvovirus of unknown species origin. The assay was able to detect as little as 10 pg of MOPV viral DNA or 1 pg of HOPV viral DNA, and it was able to detect MOPV in tissues from naturally infected mice and HOPV in tissues from experimentally infected hamsters. In contrast, the 260-bp product was not amplified from tissues of MOPV-negative mice or mock-infected hamsters. Our findings indicate that this PCR assay provides a rapid, specific, and sensitive method for the detection of MOPV in mice, HOPV in hamsters, and MOPV and HOPV in cell culture systems and that it may also be useful for the detection of LuIII contamination of cell culture systems.

Animals↗

Prolonged parvovirus b19 viremia in spite of neutralizing antibodies after erythema infectiosum in pregnancy.

OBJECTIVE: To check the clearance of parvovirus B19 in the course of the development of neutralizing antibodies after Erythema infectiosum in pregnancy. METHODS: Parvovirus B19 serology (Parvovirus B19 IFA IgG, IgM Antibody Test Kit, Biotrin, Ireland and Immunoblot RIDA Blot Parvovirus B19, R-Biopharm, Germany) and polymerase chain reaction (PCR Parvovirus B19, Roche Diagnostics, Switzerland) were performed in eight predelivery sera, one cord blood sample and one serum 2 months after delivery. RESULTS: Acute parvovirus B19 infection in pregnancy was diagnosed by seroconversion in the IgM and IgG antibody class and detection of viral DNA by PCR. Despite the presence of neutralizing antibodies, PCR gave positive results in all subsequent sera including the cord blood sample and the post-delivery sample 7 months after primary infection. Neonatal examination on the 4th day after delivery was normal and no clinical sign of intrauterine infection was noted. CONCLUSIONS: Prolonged parvovirus B19 viremia infection can be seen in spite of neutralizing IgG antibodies and in IgM negative patients. Therefore, the presence of IgG antibodies in the absence of IgM antibodies should not always be interpreted as a past infection. The infectivity of patients with persistent parvovirus B19 infection requires further studies.

Adult↗

[Diagnosis of parvovirus B19 infection in hematological patients with partial red cell aplasia of the bone marrow].

AIM: To assess diagnosis of parvovirus B19 infection (PI) in patients with aplastic crises by combined use of polymerase chain reaction (PCR) and enzyme immunoassay (EIA) of specific IgM and IgG. MATERIAL AND METHODS: A total of 159 serum samples from 77 PI suspects were examined. The examination for virus DNA was conducted with modified "net" PCR in 108 samples, for specific IgM and IgG with EIA in 110 samples. RESULTS: The percentage of patients infected with parvovirus detected by PCR or EIA reached 60%. 21 of 77 patients with hemolytic anemias were infected with parvovirus B19, the virus persisting in 8 cases (40%). persistence of the virus was registered if viremia occurred in immunodeficiency due to the disease or immunosuppressive therapy. Immunity to parvovirus has not developed: IgM expression was the same as in patients without hemopoietic abnormalities, while IgG was not detected. The absence of specific immunity to parvovirus B19 occurred in patients treated with immunosuppressive drugs early after the end of viremia period in high IgM level and at the initial phase of IgG synthesis. IgM levels also remained unchanged; the level of IgG declined and was not identified furthermore. There were cases of reinfection. CONCLUSION: Combined use of PCR and EIA is optimal for diagnosis of parvovirus B19 infection in patients with hemolytic anemias. It was found that there are correlations between defects in specific immunity, persistence and immunodeficiency onset regarding viremia. Abnormal for the disease course levels of IgM and IgG indicate the persisting virus, the condition of specific immune response to parvovirus B19 and feasibility of reinfection. Reliable diagnosis of parvovirus infection is possible only in simultaneous use of PCR and EIA.

Aged↗

[Prenatal parvovirus B19 infection in fetus].

OBJECTIVE: To analyse 3 cases of parvovirus B19 infection in a pregnant woman followed by transplacental transmission to the fetus. DESIGN: A reprospective study. SETTING: Department of Obstetrics and Gynecology, University Hospital, Olomouc. METHOD: Parvovirus B19 vertical transmission from a pregnant woman to the fetus was diagnosed in 3 cases. Serologic testing of IgG and IgM antibodies against parvovirus B19, cytological bone marrow examination and parvovirus B19 DNA analysis by PCR methods were performed. The fetal anemia was predicted by measurements of peak systolic velocities in the middle cerebral artery (MCA-PSV). RESULTS: There were three pregnancies in all (1st - single, 2nd and 3rd - dizygotic twins). In the 1st and 2nd pregnancy the diagnosis of parvovirus B19 infection was set on the basis of erythroblastopenia diagnosed in the neonatal period or early infancy. In the 2nd pregnancy (dizygotic twins) intrauterine death of one twin occured. In the 3rd case (dizygotic twins) the diagnosis was already set in the 20th week of pregnancy. Subsequently the fetal anemia was predicted by doppler examination. The fetuses did not require invasive intrauterine intervention and mild anemia was diagnosed after delivery. Progressive intrauterine growth retardation of one twin was observed. Neither cardiomegaly nor fetal hydrops did not occur. All mothers were asymptomatic during the whole pregnancy. CONCLUSION: Parvovirus B19 infection should be excluded in all cases of nonimmune fetal hydrops, severe fetal anemia, cardiomegaly, intrauterine growth retardation (IUGR) and chronic erythroblastopenia diagnosed in the neonatal period or early infancy. The presence of IgM and IgG antibodies against parvovirus B19 is highly specific but their negativity is insufficient for the exclusion of a parvovirus B19 infection. Viral DNA testing by PCR method is the only reliable method available.

Adult↗

Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis.

Recent clinical observations support the hypothesis that persistent parvovirus B19 is a triggering factor of rheumatoid arthritis (RA) in certain genetically predisposed individuals. If this hypothesis is correct, a number of RA patients may exhibit parvovirus B19 DNA in their synovial membranes. We tested the synovial tissue and peripheral blood leukocytes of 20 patients with RA, 24 patients with other arthritides or osteoarthritis (non-RA), and 34 healthy blood donors for the presence of parvovirus B19 DNA using specific DNA amplification by polymerase chain reaction (PCR). Using this technique, parvovirus B19 DNA was demonstrated in the synovial biopsies of 75% of patients with RA but in those of only 16.7% of patients with non-RA. In autologous peripheral blood mononuclear cells the percentage of PCR-positive patients was about 15% in both RA and non-RA groups and did not differ from that in healthy controls. When the PCR data were correlated with the presence of anti-parvovirus B19 IgG antibodies in serum and synovia all patients with parvovirus B19 DNA in peripheral blood alone or in both peripheral blood and synovial membrane were seropositive. In contrast, about 40% of patients with parvovirus B19 DNA restricted to the synovial membrane were seronegative. These data indicate a highly disease-related persistence of parvovirus B19 in the rheumatoid synovium.

Antigen-Antibody Reactions↗

The structure of an insect parvovirus (Galleria mellonella densovirus) at 3.7 A resolution.

BACKGROUND: Parvoviruses infect vertebrates, insects and crustaceans. Many arthropod parvoviruses (densoviruses) are highly pathogenic and kill approximately 90% of the host larvae within days, making them potentially effective as selective pesticides. Improved understanding of densoviral structure and function is therefore desirable. There are four different initiation sites for translation of the densovirus capsid protein mRNA, giving rise to the viral proteins VP1 to VP4. Sixty copies of the common, C-terminal domain make up the ordered part of the icosahedral capsid. RESULTS: The Galleria mellonella densovirus (GMDNV) capsid protein consists of a core beta-barrel motif, similar to that found in many other viral capsid proteins. The structure most closely resembles that of the vertebrate parvoviruses, but it has diverged beyond recognition in many of the long loop regions that constitute the surface features and intersubunit contacts. The N termini of twofold-related subunits have swapped their positions relative to those of the vertebrate parvoviruses. Unlike in the vertebrate parvoviruses, in GmDNV there is no continuous electron density in the channels running along the fivefold axes of the virus. Electron density corresponding to some of the single-stranded DNA genome is visible in the crystal structure, but it is not as well defined as in the vertebrate parvoviruses. CONCLUSIONS: The sequence of the glycine-rich motif, which occupies each of the channels along the fivefold axes in vertebrate viruses, is conserved between mammalian and insect parvoviruses. This motif may serve to externalize the N-terminal region of the single VP1 subunit per particle. The domain swapping of the N termini between insect and vertebrate parvoviruses may have the effect of increasing capsid stability in GmDNV.

Amino Acid Sequence↗

Successful high-titer immunoglobulin therapy for persistent parvovirus B19 infection in a lymphoma patient treated with rituximab-combined chemotherapy.

A 40-year-old female diagnosed with follicular lymphoma was treated with rituximab-combined chemotherapy. Although she achieved complete remission, she developed progressive anemia and reticulocytopenia. Bone marrow examination revealed features of pure red cell aplasia and hemophagocytosis. In addition, the appearance of large pronormoblasts suggested that she was infected with parvovirus B19. Excess viral DNA in her bone marrow confirmed that her illness was caused by persistent parvovirus B19 infection. Serum immunoglobulin levels decreased beyond the lower normal limit, which indicated that her humoral immunity was impaired after rituximab-combined chemotherapy. Although she had been infected with parvovirus B19, she was re-infected and failed to control the viral expansion. High-titer immunoglobulin against parvovirus B19 was intravenously administrated and resulted in remarkable reticulocytosis and improvement of anemia. High-titer immunoglobulin, which contained a sufficient amount of neutralizing antibodies against parvovirus B19, likely inactivated most viruses in vivo. We successfully eradicated the virus after 2 courses of high-dose therapy at 0.5 g/kg/day every week followed by 8 courses of maintenance therapy at 0.1 g/kg/day every other week. It is important to consider that parvovirus B19 infection is a possible cause of progressive anemia in B-cell lymphoma patients treated with rituximab-combined chemotherapy. We propose that the use of high-titer immunoglobulin against parvovirus B19 may enable such immunocompromised patients to eradicate the virus before sufficient immune system reconstruction.

Adult↗