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Since its first discovery by Arnold Theiler in 1918, serum hepatitis also known as Theiler's disease has been reported worldwide, causing idiopathic acute hepatitis and liver failure in horses. Recent studies have suggested a novel parvovirus, named equine parvovirus hepatitis (EqPV-H), to be associated with Theiler's disease. Despite the severity and potential fatality of EqPV-H infection, little is known about the possibility of developing chronic infections and putative cross-species infection of equine sister species. In the present longitudinal study, we employed qPCR analysis, serology, and biochemical testing as well as pathology examination of liver biopsies and sequence analysis to investigate potential chronic EqPV-H infection in an isolated study cohort of in total 124 horses from Germany over five years (2013-2018). Importantly, our data suggest that EqPV-H viremia can become chronic in infected horses that do not show biochemical and pathological signs of liver disease. Phylogenetic analysis by maximum likelihood model also confirms high sequence similarity and nucleotide conservation of the multidomain nuclear phosphoprotein NS1 sequences from equine serum samples collected between 2013-2018. Moreover, by examining human, zebra, and donkey sera for the presence of EqPV-H DNA and VP1 capsid protein antibodies, we found evidence for cross-species infection in donkey, but not to human and zebra. In conclusion, this study provides proof for the occurrence of persistent EqPV-H infection in asymptomatic horses and cross-species EqPV-H detection in donkeys.

Canine parvovirus (CPV) has been used in cancer control as a drug delivery vehicle or anti-tumor reagent due to its multiple natural advantages. However, potential host cell cycle arrest induced by virus infection may impose a big challenge to CPV associated cancer control as it could prevent host cancer cells from undergoing cell lysis and foster them regain viability once the virotherapy was ceased. To explore CPV-induced cell cycle arrest and the underlying mechanism toward improved virotherapeutic design, we focus on epidermal growth factor receptor (EGFR), a cellular receptor interacting with TfR that mediates CPV-host interactions, and alterations on its tyrosine phosphorylation sites in response to CPV infection. We found that CPV could trigger host G1/S cell cycle arrest via the EGFR (Y1086)/p27 and EGFR (Y1068)/STAT3/cyclin D1 axes, and EGFR inhibitor could not reverse this process. Our results contribute to our understandings on the mechanism of CPV-induced host cellular response and can be used in the onco-therapeutic design utilizing CPV by preventing host cancer cells from entering cell cycle arrest.

A 70-year-old woman was admitted to our hospital for dyspnea and a fever of 2 weeks duration. Chest imaging showed bilateral infiltration, and a rapid diagnostic test for influenza virus, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Legionella spp. was negative. She was intubated and mechanically ventilated and underwent bronchoalveolar lavage. Bronchoalveolar lavage fluid yielded no significant pathogens, and the multiplex polymerase chain reaction test was positive only for human bocavirus. Specific antibodies against significant pathogens were not increased in paired sera, so we diagnosed her with primary human bocavirus pneumonia.

Viral respiratory tract infections have been implicated as the predominant risk factor for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to evaluate, longitudinally, the association between upper respiratory tract infections (URTI) caused by viruses and AECOPD.Detection of 18 viruses was performed in naso- and orοpharyngeal swabs from 450 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) who were followed for a mean of 27 months. Swabs were taken during stable periods (n=1909), at URTI onset (n=391), 10 days after the URTI (n=356) and during an AECOPD (n=177) and tested using a multiplex nucleic acid amplification test.Evidence of at least one respiratory virus was significantly higher at URTI onset (52.7%), 10 days after the URTI (15.2%) and during an AECOPD (38.4%), compared with the stable period (5.3%, p<0.001). During stable visits, rhinovirus accounted for 54.2% of all viral infections, followed by coronavirus (20.5%). None of the viruses were identified in two consecutive stable visits. Patients with a viral infection at URTI onset did not have a higher incidence of exacerbation than patients without viral infection (p=0.993). Τhe incidence of any viral infection during an AECOPD was similar between URTI-related AECOPD and non-URTI-related AECOPD (p=0.359). Only 24% of the patients that had a URTI-related AECOPD had the same virus at URTI onset and during an AECOPD. Detection of parainfluenza 3 at URTI onset was associated with a higher risk of an AECOPD (p=0.003). Rhinovirus and coronavirus were the most frequently detected viruses during AECOPD visits, accounting for 35.7% and 25.9% of all viral infections, respectively.The prevalence of viral infection during the stable period of COPD was low. The risk of exacerbation following the onset of URTI symptoms depends on the particular virus associated with the event and was significant only for parainfluenza 3., Competing Interests: Conflict of interest: D. Stolz has nothing to disclose. Conflict of interest: E. Papakonstantinou has nothing to disclose. Conflict of interest: L. Grize has nothing to disclose. Conflict of interest: D. Schilter has nothing to disclose. Conflict of interest: W. Strobel has nothing to disclose. Conflict of interest: R. Louis has nothing to disclose. Conflict of interest: C. Schindler has nothing to disclose. Conflict of interest: H.H. Hirsch has nothing to disclose. Conflict of interest: M. Tamm has nothing to disclose., (Copyright ©ERS 2019.)

Parvovirus B19 (B19V) has been proposed as a triggering agent for some autoimmune diseases including systemic sclerosis (SSc). In this study, we investigated whether B19V infection in vitro differently activates inflammatory pathways, including those dependent on caspase-1 activation, in monocytes from patients with SSc and healthy controls. We showed that B19V can infect both THP-1 cells and primary monocytes but is not able to replicate in these cells. B19V infection increases the production of tumor necrosis factor-α and induces NLRP3-mediated caspase-1 activation in both THP-1 cells differentiated with phorbol 12-myristate 13-acetate and in monocytes from patients with SSc but not from healthy controls. B19V infection was sufficient for THP-1 to produce mature IL-1β. Monocytes from patients with SSc required an additional stimulus, here represented by lipopolysaccharides, to activate cytokine genes. Following B19V infection, however, lipopolysaccharide-activated monocytes from patients with SSc strongly increased the production of IL-1β and tumor necrosis factor-α. Altogether, these data suggest that viral components might potentiate the response to endogenous and/or exogenous toll-like receptor 4 ligands in monocytes from patients with SSc. The B19V-mediated activation of inflammatory pathways in monocytes might contribute to the disease progression and/or development of specific clinical phenotypes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Viral infection-associated kidney diseases are an emerging public health issue in both developing and developed countries. Many new viruses have emerged with new paradigms of kidney injury, either directly through their cytopathic effect or indirectly through immune-mediated glomerulopathy, tubulointerstitial disease, and acute kidney injury as part of multiorgan failure. Herein, we will discuss Parvovirus, which causes glomerulopathy, and Hanta, Ebola, and Dengue viruses, which cause viral hemorrhagic fever and acute kidney injury. Clinical manifestations also depend on extrarenal organ systems involved. Diagnosis of these viral infections is mainly based on a high index of suspicion, serologic testing, and isolation of viral DNA/RNA. Management is largely conservative, as specific antiviral agents are unavailable., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: There are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients the idea of infective agents as trigger must be considered., Case Presentation: We describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis. The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions. Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%). He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister's history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome., Conclusions: We report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction. We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.

Background: To describe extra-haematological manifestations associated with human parvovirus B19 (HPV-B19) infection., Methods: We conducted a nationwide multicentre study to retrospectively describe the characteristics and outcome of extra-haematological manifestations in French adults., Results: Data from 25 patients followed from 2001 to 2016 were analysed. Median age was 37.9 years (range: 22.7-83.4), with a female predominance (sex ratio: 4/1). Only 3 patients had an underlying predisposing condition (hemoglobinopathy or pregnancy). The most common manifestations were joint (80%) and skin (60%) involvement. Four patients (16%) had renal involvement (endocapillary proliferative or membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis). Three patients (12%) had peripheral nervous system involvement (mononeuritis, mononeuritis multiplex, Guillain-Barré syndrome) and 2 (8%) presented muscle involvement. Other manifestations included hemophagocytic lymphohistiocytosis (n = 1), myopericarditis and pleural effusion (n = 1), and lymphadenopathy and splenomegaly mimicking lymphoma with spleen infarcts (n = 1). Immunological abnormalities were frequent (56.5%). At 6 months, all patients were alive, and 54.2% were in complete remission. In 2 patients, joint involvement evolved into rheumatoid arthritis. Six patients (24%) received intravenous immunoglobulin (IVIg), with a good response in the 3 patients with peripheral nervous system involvement., Conclusions: HPV-B19 infection should be considered in a wide range of clinical manifestations. Although the prognosis is good, IVIg therapy should be discussed in patients with peripheral nerve involvement. However, its efficacy should be further investigated in prospective studies.

Three parvoviruses were isolated from the raccoon dogs experiencing severe enteritis, named RDPV-DP1, RDPV-DP2 and RDPV-DP3, respectively. The VP2 genes of the 3 isolates showed 99.9% identity at the nucleotide level, and shared 99.1%-99.5% identity with the reference CPVs. The RDPVs resembled original CPV-2, but with four mutations. The RDPVs displayed S297A of VP2 protein as CPV-2a or CPV-2b prevalent throughout most of the world. Residue N375D was found in the 3 isolates, resembling CPV-2a/2b/2c. And the 3 isolates had a natural mutation of VP2 residue V562L, which is adjacent to residue 564 and 568 and might be involved in host range. Interestingly, VP2 S27T was firstly found in the isolates. Phylogenetic analysis of VP2 genes revealed that the RDPVs were clustered into one small evolutionary branch and shared the identical branch with 7 CPV-2 isolates from raccoon dogs and one CPV-2 isolate from fox, not with CPV vaccine viruses. Phylogenetic analysis of NS1 genes demonstrated that the RDPVs shared the identical branch with the reference CPV-2a/2b/2c. Experimental infection showed that RDPV infection caused a high morbidity in raccoon dogs. It implied that the RDPV was virulent to raccoon dogs and continued to evolve in China., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Parvovirus B19 (PVB19) has rarely been identified as a cause of encephalitis in immunocompetent adults, in whom clinical information regarding PVB19 encephalitis has remained unclear. Herein, we report the clinical presentations, laboratory and imaging findings, and treatment outcomes of five immunocompetent adults with PVB19 encephalitis. Although none of the patients showed any distinctive features of PVB19 infection, they showed various clinical manifestations, including one instance of brainstem involvement. Additionally, immunotherapy can be considered an effective approach, especially in immunocompetent adults with PVB19 encephalitis who are resistant to the initial management.

Background: So far, many studies have shown that Human Bocavirus ( HBoV) is the main pathogen of the respiratory tract. Until now, there is no study that proves the association between HBoV and hepatitis. HBoV viremia/DNAemia has been associated closely with acute primary infection and moderate-to-severe illness but, more detailed clinical data about HBoV dissemination are still unavailable., Case Report: Here we report a 2-years-5-months-old girl suffering from respiratory distress and heptitis followed in our intensive care unit. HBoV was detected in our patients nose and throat swabs concurrent with whole blood sample by positive polymerase chain reactions. After a through investigation no causative agent other than HBoV viremia was found., Conclusion: Human Bocavirus viremia with high viral loads may be associated with hepatitis.

Background: Meningococcal infection is a multifaceted disease including acute polyarthritis. This presentation should be known by clinicians in order to prevent delay in treatment. We report what we believe to be the first case of an association of parvovirus B19 and meningococcal polyarthritis in a young adult., Case Presentation: A 19-year-old Caucasian woman presented to our hospital with fever, intense leg pain, and a transient rash. A physical examination showed asymmetric polyarthritis and no neurological abnormalities. A parvovirus B19 polymerase chain reaction performed using a blood sample and knee fluid aspirate came back positive, but serology was negative for immunoglobulin M and positive for immunoglobulin G. A blood culture was positive for serotype C meningococcus; a polymerase chain reaction performed for Neisseria meningitidis was positive in joint fluid but negative in blood samples (performed after antibiotic treatment had begun). Our patient was treated with ceftriaxone for 15 days, associated with analgesic therapy. Hydroxychloroquine treatment was introduced 5 months after the onset of polyarthritis because of persisting inflammatory arthralgia., Conclusions: To the best of our knowledge, this is the first case report of polyarthritis caused by concomitant meningococcal and parvovirus B19 infections. This unusual presentation of meningococcal disease may have resulted from the persistent parvovirus B19 infection. Our experience with this case illustrates the need for a systematic approach to the diagnosis of febrile acute polyarthritis. Only long-term follow-up will reveal if this infectious polyarthritis will evolve towards an autoimmune rheumatism.

Objectives: A vendor informed us that rats shipped to us and used by us in a spinal cord contusion injury experiment were infected by rat parvovirus type 1a (RPV-1a). Our aim was therefore to determine whether this infection may have altered locomotor recovery or tissue pathology., Setting: Stockholm, Sweden., Methods: We induced a moderate contusion injury of the spinal cord in rats received from an (unknown to us) RPV-1a-contaminated facility. We compared the hind limb locomotor function between RPV-1a-infected rats and non-infected controls with the same spinal cord lesions, obtained before (historical control), as well as after infection (future controls). Histologically, we assessed spinal tissue sparing, astrocyte reactivity and the amount of macrophages/activated microglia., Results: RPV-1a-infected rats had significantly better hind limb locomotor recovery compared with both 'historical' and 'future' controls. We also observed significantly better tissue sparing and axonal sparing around the injury site, as well as significant reductions in macrophages/activated microglia and astrocyte reactivity in the spinal cords of RPV-1a-infected rats., Conclusion: The results stress the importance of knowing the health status of animals used to study central nervous system trauma and support the notion that acquired infections, even if asymptomatic, may alter response to injury in mammals. Furthermore, the results demonstrate that virus infections may have positive effects on functional recovery after spinal cord injury and indicate that RPV-1a infection may be neuroprotective by dampening secondary damage.

Background: The advent of PCR testing for the presence of viral genomes has led to the identification of parvovirus B19 (PVB19) as a causative agent of myocarditis., Methods: The clinical presentation, course and outcome of children with PVB19 myocarditis was ascertained through a retrospective review. The PVB19 viral genome was detected by PCR from whole blood or endomyocardial biopsy specimens in patients presenting with new onset heart failure., Results: Seventeen patients presented at a median age of 1.3 years (range: 0.4-15.4 years) in cardiac failure with a mean fractional shortening of 15±3%. Eleven patients required mechanical ventilation and intravenous inotropes and seven required extra-corporeal mechanical oxygenation. Four of the five deaths occurred in patients who had a short prodromal illness of less than 48 hours. All patients with ST segment elevation died (n=4). All non-fulminant cases survived. Event-free survival occurred in 11/17 (65%) patients. Five (29%) patients died and one patient underwent heart transplantation. Complete recovery of cardiac function occurred within a median of 12 months (range: 1-48) in five patients. There was incomplete recovery in five patients and one patient had persistent dilated cardiomyopathy., Conclusions: PVB19 can cause a devastating myocarditis in children. Children with fulminant myocarditis, ST segment changes or a short prodrome have the worst outcome. Transplantation may be considered, but is rarely required in the acute period if mechanical circulatory support is utilised. If the initial presentation is survived, recovery of the myocardium can occur even in those who had fulminant myocarditis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV-negative patients were analysed by semi-quantitative Western spot blot analyses. Although lots of cytokines were regulated independently of HBoV status, several cytokines associated with lung fibrosis and tumour development, e.g., EGF, VEGF, TARC (CCL17), TNF-α, TNF-β, TIMP-1, were clearly upregulated in the HBoV-positive cohort. These findings suggest that the development of lung fibrosis might be triggered by HBoV induced cytokine expression.

Objective: Primary objective was to establish the prognostic value of the myocardial load of PVB19 genomes in patients presenting for work-up of myocarditis and/or unclear cardiomyopathy in comparison to clinical, and CMR parameters., Methods: 108 consecutive patients who underwent EMB because of suspected myocarditis and/or unclear cardiomyopathy, and had evidence of myocardial PVB19 genome, were enrolled. Primary endpoint was all-cause mortality; secondary endpoint was a composite of cardiac mortality and hospitalization for heart failure., Results: Mean LV-EF was 40%. We found n = 27 patients to have a viral load ≥ 500 GE (IQR 559-846), n = 72 had 100-499 GE, and n = 9 had <100 GE. Immunohistology revealed chronic myocarditis in n = 66, acute myocarditis in n = 1, DCM in n = 17, PVB19 genome only in n = 13, and other pathologies in n = 11. During follow-up 11 patients died, two suffered SCD but were successfully shocked by ICD, and 21 were hospitalized for heart failure. Interestingly, not the viral load, but functional parameters such as LV-EF, LV-EDV (endpoint 2), as well as the histologic diagnosis of DCM and the presence of LGE (for all endpoints) reached statistical significance. In fact, the presence of LGE yields an odds-ratio for a lethal event of 8.56 (endpoint 1), and of 5.52 for endpoint 2. No patient with normal LV-EF, or the absence of LGE, suffered cardiac death during long-term follow-up., Conclusion: The viral load of PVB19 genomes in the myocardium is not related to the long-term outcome. Furthermore, this study suggests a growing role of imaging for risk stratification in non-ischemic myocardial disease.

Until now, more than seventeen parvovirus have been reported which can infect mammals and poultries. The infected cells appeared different properties of apoptosis and death, present a typical cytopathic effect. NS1 is a major nonstructural protein of parvovirus, with a conservative structure and function, which plays an important role in the viral life cycle. In addition to the influence on viral replication, the NS1 also participates in apoptosis induced by viruses. Parvovirus induced apoptosis which is mainly mediated by mitochondrial pathway, this review summarized the latest research progresses of parvovirus induced apoptosis.

"Small virus" contagious during spring, parvovirus B19 is responsible for fifth disease of children. The prevalence of infection is very high before 10 years old and children are especially responsible for transmission to pregnant women. Approximately 50% of women old enough to procreate have stigmas serologic of old infection. Acquired immunity is long hasting and solid. During pregnancy, this virus is responsible for abortion, fetal anemia. Severe anemia can cause hydrops fetalis or fetal mortality in utero or neurologic damage. We are going to start again point by point of the contage has the care the situations with which the doctor can be confronted during the pregnancy., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

This study characterized the effects of challenge with a field isolate of mouse parvovirus 1 (MPV1e) in C57BL/6NCrl (B6) and BALB/cAnNCrl (C) mice. We found that C mice were more susceptible to MPV1e infection than were B6 mice; ID50 were 50 to 100 times higher after gavage and 10-fold higher after intraperitoneal injection in B6 as compared with C mice. To evaluate the host strain effect on the pathogenesis of MPV1e, B6 and C mice were inoculated by gavage. Feces and tissues, including mesenteric lymph nodes (MLN), ileum, spleen and blood, were collected for analysis by quantitative PCR (qPCR) to assess infection and fecal shedding and by RT-qPCR to evaluate replication. Peak levels of MPV1e shedding, infection, and replication were on average 3.4, 4.3, and 6.2 times higher, respectively, in C than in B6 mice. Peaks occurred between 3 and 10 d after inoculation in C mice but between 5 and 14 d in B6 mice. Multiplexed fluorometric immunoassays detected seroconversion in 2 of 3 C mice at 7 d after inoculation and in all 3 B6 mice at 10 d. By 56 d after inoculation, viral replication was no longer detectable, and fecal shedding was very low; infection persisted in ileum, spleen, and MLN, with levels higher in C than B6 mice and highest in MLN. Therefore, the lower susceptibility of B6 mice, as compared with C mice, to MPV1e infection was associated with lower levels of infection, replication, and shedding and delayed seroconversion.

While most parvovirus B19 or HHV-6 infections resolve without sequelae, rheumatologic and hemolytic complications and seizures can develop.

Parvovirus B19 has been linked with various clinical syndromes including neurological manifestations. However, its role in the latter remains not completely understood. Although the last 10 years witnessed a surge of case reports on B19-associated neurological aspects, the literature data remains scattered and heterogeneous, and epidemiological information on the incidence of B19-associated neurological aspects cannot be accurately extrapolated. The aim of this review is to identify the characteristics of cases of B19-associated neurological manifestations. A computerized systematic review of existing literature concerning cases of B19-related neurological aspects revealed 89 articles describing 129 patients; 79 (61.2%) were associated with CNS manifestations, 41 (31.8%) were associated with peripheral nervous system manifestations, and 9 (7.0%) were linked with myalgic encephalomyelitis. The majority of the cases (50/129) had encephalitis. Clinical characteristic features of these cases were analyzed, and possible pathological mechanisms were also described. In conclusion, B19 should be included in differential diagnosis of encephalitic syndromes of unknown etiology in all age groups. Diagnosis should rely on investigation of anti-B19 IgM antibodies and detection of B19 DNA in serum or CSF. Treatment of severe cases might benefit from a combined regime of intravenous immunoglobulins and steroids. To confirm these outcomes, goal-targeted studies are recommended to exactly identify epidemiological scenarios and explore potential pathogenic mechanisms of these complications. Performing retrospective and prospective and multicenter studies concerning B19 and neurological aspects in general, and B19 and encephalitic syndromes in particular, are required., (© 2014 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd.)

Objective: We investigated the incidence of human parvovirus B19 (HPV B19) infection after renal transplantation as well as the risk of anemia and renal allograft damage among infected transplant recipients in China., Methods: We selected 114 patients at 1-18 months after renal transplantation for detection of HPV B19 DNA copies compared with a control population. Renal function and hematopoiesis were compared between infected and noninfected groups., Results: Twenty-seven patients diagnosed with HPV B19 infection during follow-up (18.75%),which was a significantly higher number than among the general population over the same period. Infected versus nonaffected patients exhibited a significantly higher incidence of anemia and urinary abnormalities in addition to significantly lower values of hemoglobin, higher serum creatinine concentrations, and lower glomerular filtration rates. The 2 groups did not differ in the types or doses of calcineurin inhibitor (CNI) immunosuppressants. Two cases of pure red cell aplasia (PRCA) as confirmed using bone marrow biopsy, were observed in the infected group. They displayed HPV B19 DNA copy numbers >10(7)/mL and segmental mesangial cell proliferation on renal biopsy. The PRCA cases were cured with immunomodulatory therapy., Conclusions: The HPV B19 infection rate was significantly higher among renal transplant recipients than normal controls. Infections correlated with damage to the renal allograft, which may in turn cause PRCA. Immunomodulation therapy was effective to treat this complication of HPV B19 infection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

An 11-year-old boy presented with epistaxis, petechial hemorrhages, easy bruising, and purpuric rash. He was diagnosed to have immune thrombocytopenic purpura and evidence of concomitant parvovirus B19 and dengue viral infection.

Activation of a host DNA damage response (DDR) is essential for DNA replication of minute virus of canines (MVC), a member of the genus Bocavirus of the Parvoviridae family; however, the mechanism by which DDR contributes to viral DNA replication is unknown. In the current study, we demonstrate that MVC infection triggers the intra-S-phase arrest to slow down host cellular DNA replication and to recruit cellular DNA replication factors for viral DNA replication. The intra-S-phase arrest is regulated by ATM (ataxia telangiectasia-mutated kinase) signaling in a p53-independent manner. Moreover, we demonstrate that SMC1 (structural maintenance of chromosomes 1) is the key regulator of the intra-S-phase arrest induced during infection. Either knockdown of SMC1 or complementation with a dominant negative SMC1 mutant blocks both the intra-S-phase arrest and viral DNA replication. Finally, we show that the intra-S-phase arrest induced during MVC infection was caused neither by damaged host cellular DNA nor by viral proteins but by replicating viral genomes physically associated with the DNA damage sensor, the Mre11-Rad50-Nbs1 (MRN) complex. In conclusion, the feedback loop between MVC DNA replication and the intra-S-phase arrest is mediated by ATM-SMC1 signaling and plays a critical role in MVC DNA replication. Thus, our findings unravel the mechanism underlying DDR signaling-facilitated MVC DNA replication and demonstrate a novel strategy of DNA virus-host interaction.

Previously we identified a novel parvovirus from enteric contents of chickens that were affected by enteric diseases. Comparative sequence analysis showed that the chicken parvovirus (ChPV) represented a new member in the Parvoviridae family. Here, we describe some of the pathogenic characteristics of ChPV in young broilers. Following experimental infection, 2-day-old broiler chickens showed characteristic signs of enteric disease. Runting-stunting syndrome (RSS) was observed in four of five experimental groups with significant growth retardation between 7 and 28 days postinoculation (DPI). Viral growth in small intestine and shedding was detected at early times postinoculation, which was followed by viremia and generalization of infection. ChPV could be detected in most of the major tissues for 3 to 4 wk postinoculation. Immunohistochemistry staining revealed parvovirus-positive cells in the duodenum of inoculated birds at 7 and 14 DPI. Our data indicate that ChPV alone induces RSS in broilers and is important determinant in the complex etiology of enteric diseases of poultry.

Objective: To determin the extent to which parvovirus B19 (B19V) and co-infection of B19V and malaria contribute to risk of anaemia in children., Methods: B19V DNA and malaria parasites were screened for 234 children at the PML Children's Hospital in Accra. The role of B19V and co-infection with B19V and malaria in anaemia was evaluated by analysing full blood cell counts, malaria and B19V DNA results from these children., Results: The prevalence of B19V, malaria and co-infection with B19V and malaria was 4.7%, 41.9% and 2.6%, respectively. Malaria posed a greater risk in the development of mild anaemia compared to severe anaemia (OR=5.28 vrs 3.15) whereas B19V posed a higher risk in the development of severe anaemia compared to mild anaemia (OR=4.07 vrs 1.00) from a non-anaemic child. Persons with co-infection with B19V and malaria had 2.23 times the risk (95% CI=0.40-12.54) of developing severe anaemia should they already have a mild anaemia. The degree of anaemia was about three times affected by co-infection (Pillai's trace=0.551, P=0.001) as was affected by malaria alone (Pillai's trace=0.185, P=0.001). B19V alone did not significantly affect the development of anaemia in a non-anaemic child. Microcytic anaemia was associated with B19V and co-infection with B19V and malaria more than normocytic normochromic anaemia., Conclusions: B19V was associated with malaria in cases of severe anaemia. The association posed a significant risk for exacerbation of anaemia in mild anaemic children. B19V and co-infection with B19V and malaria may be associated with microcytic anaemia rather than normocytic normochromic anaemia as seen in cases of B19V infection among persons with red cell abnormalities.

Introduction: The incidence of human parvovirus B19 infection is unknown., Aim: A retrospective analysis of clinical and laboratory findings was carried out in patients diagnosed with human parvovirus B19 infection in 2011 in a virologic laboratory of a single centre in Hungary., Methods: Clinical and laboratory data of patients with proven human parvovirus B19 infection were analysed using in- and out-patient files., Results: In 2011, 72 patients proved to have human parvovirus B19 infection with the use of enzyme immunoassay. The clinical diagnoses of these patients were as follows: human parvovirus B19 infection (30.6%), transient aplastic crisis (16.7%), arthritis (8.3%) and acute hepatitis (4.1%). Symptoms of each of the four phases of the infection occurred in various combinations with the exception of the monophase of cheek exanthema. This occurred without the presence of other symptoms in some cases. Leading symptoms and signs were exanthema (in 74.6% of cases), haematological disorders (in 69% of cases), fever (in 54.9% of cases) and arthritis (in 33.8% of cases). Several atypical dermatological symptoms were also observed. Acute arthritis without exanthema was noted in 8 patients. Of the 72 patients with proven human parvovirus B19 infection there were 7 pregnant women, and one of them had hydrops foetalis resulting spontaneous abortion. In 16 patients (22.5%) human parvovirus B19 IgG was undetectable despite an optimal time for testing., Conclusion: The observations of this study may contribute to a better recognition of clinical symptoms of human parvovirus B19 infection.

Cell specific gene transfer and sustained transgene expression are goals of cutaneous gene therapy for tissue repair and regeneration. Adeno-associated virus serotype 2 (AAV2/2) mediated gene transfer to the skin results in stable transgene expression in the muscle fascicles of the panniculus carnosus in mice, with minimal gene transfer to the dermal or epidermal elements. We hypothesized that pseudotyped AAV vectors may have a unique and characteristic tropism and transduction efficiency profile for specific cells in the cutaneous wounds. We compared transduction efficiencies of cells in the epidermis, cells in the dermis, and the fascicles of the panniculus carnosus by AAV2/2 and three pseudotyped AAV vectors, AAV2/5, AAV2/7, and AAV2/8 in a murine excisional wound model. AAV2/5 and AAV2/8 result in significantly enhanced transduction of cells both in the epidermis and the dermis compared to AAV2/2. AAV2/5 transduces both the basilar and supra-basilar keratinocytes. In contrast, AAV2/8 transduces mainly supra-basilar keratinocytes. Both AAV2/7 and AAV2/8 result in more efficient gene transfer to the muscular panniculus carnosus compared to AAV2/2. The capsid of the different pseudotyped AAV vectors produces distinct tropism and efficiency profiles in the murine wound healing model. Both AAV2/5 and AAV2/8 administration result in significantly enhanced gene transfer. To further characterize cell specific transduction and tropism profiles of the AAV pseudotyped vectors, we performed in vitro experiments using human and mouse primary dermal fibroblasts. Our data demonstrate that pseudotyping strategy confers a differential transduction of dermal fibroblasts, with higher transduction of both human and murine cells by AAV2/5 and AAV2/8 at early and later time points. At later time points, AAV2/2 demonstrates increased transduction. Interestingly, AAV2/8 appears to be more efficacious in transducing human cells as compared to AAV2/5. The pseudotype-specific pattern of transduction and tropism observed both in vivo and in vitro suggests that choice of AAV vectors should be based on the desired target cell and the timing of transgene expression in wound healing for gene transfer therapy in dermal wounds., (© 2012 by the Wound Healing Society.)

Objective: To investigate the effects of canine parvovirus (CPV) non-structural protein-1 (NS1) on the cell apoptosis induced by CPV and preliminarily explore the mechanism of CPV-induced apoptosis., Methods: First, the NS1 gene was amplified by PCR from CPV genomic DNA and subcloned into pcDNA3. 1A vector to generate NS1 eukaryotic expression vector pcDNA-NS1. To verify whether pcDNA-NS1 vector can mediate NS1 expression in eukaryotic cells, the human embryo kideny (HEK) 293FT cells were used to transiently express the recombinant NS1. The effects of NS1 on CPV-induced apoptosis were investigated by infecting the F81 host cells with CPV and transfecting the cells with NS1 vector. The apoptosis of the cells was detected by AnnexinV/PI double staining for phosphatidylserine externalization on membrane and by luminescence method for caspase-3/7 activities., Results: The results show that the sequence of NS1 gene amplified was consistent with the GenBank. The NS1 expression vector was shown to be correct and could mediate NS1 expression in eukaryotic cells. The phosphatidylserine on outside of membrane was detected and the caspase-3/7 activities were increased in both CPV-infected cells and NS1-transfected cells. These results indicate that both CPV and NS1 protein can induce the apoptosis of the cells., Conclusion: CPV-induced apoptosis was closely related to its non-structural protein NS1.

Adeno-associated viruses (AAVs) are nonpathogenic, nonenveloped, single-stranded DNA viruses in development as gene therapy vectors. AAV internalization was postulated to proceed via a dynamin-dependent endocytic mechanism. Revisiting this, we find that infectious endocytosis of the prototypical AAV, AAV2, is independent of clathrin, caveolin, and dynamin. AAV2 infection is sensitive to EIPA, a fluid-phase uptake inhibitor, but is unaffected by Rac1 mutants or other macropinocytosis inhibitors. In contrast, AAV2 infection requires actin cytoskeleton remodeling and membrane cholesterol and is sensitive to inhibition of Cdc42, Arf1, and GRAF1, factors known to be involved in the formation of clathrin-independent carriers (CLIC). AAV2 virions are internalized in the detergent-resistant GPI-anchored-protein-enriched endosomal compartment (GEEC) and translocated to the Golgi apparatus, similarly to the CLIC/GEEC marker cholera toxin B. Our results indicate that-unlike the viral entry mechanisms described so far-AAV2 uses the pleiomorphic CLIC/GEEC pathway as its major endocytic infection route., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Genotype-specific effects of parvovirus B19 (B19V) infections on left ventricular function in patients with dilated cardiomyopathy (DCM) have not been investigated so far. In this prospective clinical study, the prevalences of B19V genotypes in endomyocardial biopsies from patients presenting with inflammatory heart disease and DCM were determined. A total of 139 consecutive patients were included in the study; among them 53 patients were diagnosed as DCM. Among the total study cohort, B19V DNA was detected in 65 study participants (46.8%). Genotyping of the B19V genomes in the total cohort identified genotype 1 in 38 samples (27.3%), genotype 2 in 25 samples (18.0%), and genotype 3 in only two patients (1.4%). During an average follow-up period of 8 months left ventricular ejection fraction (LVEF) improved significantly both in B19V-positive (7.1 ± 13.8%, n = 17, P = 0.038) as well as B19V-negative patients with DCM (9.5 ± 13.9%, n = 20, P = 0.017). However, mean LVEF improved only in patients with genotype 1 (11.0 ± 14.4%, n = 7), whereas it even decreased in patients with genotype 2 (-6.2 ± 6.3%, n = 5, P = 0.033). These data from a small sample of patients diagnosed as DCM suggested that myocardial function during short-time follow-up differed between genetic variants of B19V. Patients with genotype 1 were on average younger than genotype 2 and appeared to be more prone to a beneficial course of left ventricular function than patients with genotype 2. Future studies with larger sample sizes and longer follow-up periods will be required to confirm this observation., (Copyright © 2011 Wiley-Liss, Inc.)

Penaeus merguiensis densovirus (PmergDNV) is currently present on several Queensland prawn farms culturing Penaeus merguiensis. Densoviruses have been linked to mortality and stunting that has caused significant financial loss to prawn farms in Asia. A histopathological study for PmergDNV was initially undertaken to compare broodstock to grow out factors from 60 broodstock animals from each of 22 ponds. There was a significant negative correlation (r = -0.61) between the number of animals with PmergDNV lesions and healthy animals. Furthermore, a higher number of septic hepatopancreatic tubules was correlated (r = 0.48) to high PmergDNV loads. Hence, a polymerase chain reaction analysis of 10-day-old post-larvae (PL) was conducted to determine whether PmergDNV infection was resulting in production losses. An attributable risk analysis of PL from 190 ponds over a 2-year period revealed that 28-29% of ponds with below average survival will have at least average survival following the removal of or decreased levels of PmergDNV. P. merguiensis culture facilities in Queensland should have at least a 14.5% increase in production, equating to an increase of $2.25 million within the first year alone, following the removal or reduction of PmergDNV in their ponds. Hence, focussing efforts on prevention, better management practices and maintaining healthy stock should be of top priority., (© 2011 Blackwell Publishing Ltd.)

Background: Human parvovirus B19 (PVB19) infection is occasionally associated with acute myocarditis. Three cases of children with PVB19 virus-associated myocarditis occurred in a very short period and the same geographical region., Objective: To elucidate if virological factors could be responsible for determining the course of infection, a molecular epidemiologic investigation was performed., Study Design: The diagnosis of myocarditis was established by histology or echocardiography. In the three cases, the PVB19 DNA was detected in different samples. Eight different regions were amplified by PCR using a high fidelity Taq polymerase and sequenced on both strands. Phylogenetic analyses were performed. First, the genotypes of the PVB19 strains were determined, then the intra-patient viral variability was analysed by sequencing PVB19 detected in different specimens sampled from the same patient at the same moment., Results: Nearly complete sequences of the PVB19 virus (4265nt) were obtained from different samples in the three patients. The phylogenetic analyses showed that PVB19 strains identified clustered with genotype 1a PVB19 strains referenced in GenBank. When compared to the referenced strain NC&#95;000883, the number of substitutions (transitions and transversions) were as follows: 58 for Caen.FRA/19.09, 74 for Caen.FRA/21.09 and 60 for Caen.FRA/24.09. The strains isolated from the same patient showed 100% of similarity., Conclusions: Viral myocarditis is a frequently unrecognized cause of post-inflammatory cardiomyopathy. The detailed molecular analyses do not give rise to virological markers associated with myocarditis in these children., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Parvovirus B19 (B19V) infection is highly restricted to human erythroid progenitor cells. Although previous studies have led to the theory that the basis of this tropism is receptor expression, this has been questioned by more recent observation. In the study reported here, we have investigated the basis of this tropism, and a potential role of erythropoietin (Epo) signaling, in erythroid progenitor cells (EPCs) expanded ex vivo from CD34(+) hematopoietic cells in the absence of Epo (CD36(+)/Epo(-) EPCs). We show, first, that CD36(+)/Epo(-) EPCs do not support B19V replication, in spite of B19V entry, but Epo exposure either prior to infection or after virus entry enabled active B19V replication. Second, when Janus kinase 2 (Jak2) phosphorylation was inhibited using the inhibitor AG490, phosphorylation of the Epo receptor (EpoR) was also inhibited, and B19V replication in ex vivo-expanded erythroid progenitor cells exposed to Epo (CD36(+)/Epo(+) EPCs) was abolished. Third, expression of constitutively active EpoR in CD36(+)/Epo(-) EPCs led to efficient B19V replication. Finally, B19V replication in CD36(+)/Epo(+) EPCs required Epo, and the replication response was dose dependent. Our findings demonstrate that EpoR signaling is absolutely required for B19V replication in ex vivo-expanded erythroid progenitor cells after initial virus entry and at least partly accounts for the remarkable tropism of B19V infection for human erythroid progenitors.

Background: Parvovirus B19 is associated with erythema infectiosum in children or arthralgia and arthritis in adults. The virus is relatively conserved and nucleotide identity is expected in viruses that are epidemiologically related. Here, we describe the first cluster of parvovirus infection among hospital staff documented in Taiwan., Methods: Active surveillance was conducted in coronary care units (CCUs) at a 2200-bed teaching hospital for 1 month in 2007. A case defined clinically as occurring in a patient or staff in CCUs with new onset of fever or rash. Serum was tested for parvovirus B19 IgM and IgG by immunoblotting and DNA by nested polymerase chain reaction. When viremia was detected, nucleotide sequences were analyzed and compared with those of two clinical isolates. The attack rate was defined as the cumulative incidence of acute infection in CCU staff and patients during the study period., Results: Among 57 staff and 15 patients, five nurses met the clinical case definition. Three had acute infection as demonstrated by viral DNA and IgM. The attack rate was 5.3% for the staff and zero for patients. Seroprevalence rate was lower in staff than in patients (26.3%vs. 53.3%). The isolates collected from three cases were highly similar to a community isolate, and they varied with each other by 2-6 nucleotides. The isolate collected from a nurse was identical to that from her friend 3 weeks apart and was concordant with mutual transmission. A sequence with 45 nucleotide variations was identified from a staff member with chronic infection who was negative for IgM and had only weak IgG anti-VP1 reaction with immunoblotting. We did not find any patient as the source of infection., Conclusion: We identified a cluster of parvovirus infection that was caused by three circulating strains which did not support the hypothesis of transmission of a single strain in CCUs., (Copyright © 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.)

This study presents the first evidence of infection by a novel porcine bocavirus (PBoV) in Chinese swine herds. The PCR detection results showed that PBoV was significantly more prevalent in weanling piglets (69.7%, 69/99) with respiratory tract symptoms than that in other samples (0-13.6%) (P < 0.01). Sequence analysis showed that the partial VP1/2 genes were highly conserved (99-100% identity), and only five frequent nucleotide mutation positions existed in Chinese PBoV strains. These data indicate that PBoV might be an emerging virus for swine respiratory tract diseases. This study could help us to better understand the epidemiology of PBoV.

The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not pathogenic for humans and has oncotropic and oncosuppressive properties. The viral nonstructural NS1 protein is thought to mediate H-1PV cytotoxicity, but its exact contribution to this process remains undefined. In this study, we analyzed the effects of the H-1PV NS1 protein on human cell proliferation and cell viability. We show that NS1 expression is sufficient to induce the accumulation of cells in G(2) phase, apoptosis via caspase 9 and 3 activation, and cell lysis. Similarly, cells infected with wild-type H-1PV arrest in G(2) phase and undergo apoptosis. Furthermore, we also show that both expression of NS1 and H-1PV infection lead to higher levels of intracellular reactive oxygen species (ROS), associated with DNA double-strand breaks. Antioxidant treatment reduces ROS levels and strongly decreases NS1- and virus-induced DNA damage, cell cycle arrest, and apoptosis, indicating that NS1-induced ROS are important mediators of H-1PV cytotoxicity.

We evaluated saliva samples from 149 children 2 to 11 years old for human bocavirus (hBoV) DNA. hBoV was detected in saliva samples at asymptomatic enrollment in 3% (5/149) and during respiratory illness in 2% (2/106) of the cases. hBoV was detected in only 1/149 asymptomatic and 0/106 illness nasal samples.

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency affecting approximately 1 to 3 per million live male births. Patients are generally healthy until facing a viral infection such as Epstein-Barr Virus and then may develop fulminant infectious mononucleosis and die. XLP patients are also at increased risk of hemophagocytic lymphohistiocytosis (HLH), which may be triggered by assorted viruses. Here we report a novel case of HLH in a patient with XLP. Significant to his presentation is a paradoxical increase in natural killer (NK) cell activity. We hypothesize that this indicates that Parvovirus B19 activates NK cells via a signaling lymphocytic activation molecule-associated protein (SAP)-independent mechanism. Our case demonstrates an important etiology to consider in the differential diagnosis of XLP patients with nonfocal findings and febrile illnesses.

We evaluated the prevalence of human bocavirus and KI and WU polyomaviruses in pediatric intensive care patients with and without lower respiratory tract infection (LRTI). The prevalence of these viruses was 5.1%, 0%, and 2.6%, respectively, in children with LRTI and 4.8%, 4.8%, and 2.4%, respectively, in those without LRTI.

Parvovirus B19 is a single-stranded DNA virus exhibiting affinity for a variety of cell types including endothelial cells. The basis of the affinity is globoside expression, the receptor for B19. B19 endothelial cell parasitism accelerates endothelial cell apoptosis, potentially critical in inducing neoantigenicity and secondary antibody formation. A 38-year-old previously healthy male developed intestinal and cutaneous infarction, elevated creatinine phosphokinase (CPK) levels and progressive cytopenias. The basis of his clinical presentation was unclear until a skin biopsy suggested a potential role for virally mediated endothelial cell injury. Hematoxylin and eosin, immunohistochemical, immunofluorescent and reverse transcriptase in situ polymerase chain reaction studies were conducted on skin biopsies to assess for viral triggers. B19 viremia and localization of B19 RNA transcripts to vascular endothelium were uncovered. A diagnosis of catastrophic endothelial cell injury attributable to B19 infection was rendered. The patient showed significant improvement with intravenous immunoglobulin (IVIG). Parvovirus B19 is a ubiquitous virus that in the majority of affected patients remains asymptomatic. Nevertheless, because of its ability to infect endothelium it can cause severe multiorgan endothelial cell injury., (Copyright Blackwell Munksgaard 2008.)

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.