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Communications Biology Sep 2023Canine parvovirus (CPV) is an important pathogen that emerged by cross-species transmission to cause severe disease in dogs. To understand the host immune response to...
Canine parvovirus (CPV) is an important pathogen that emerged by cross-species transmission to cause severe disease in dogs. To understand the host immune response to vaccination, sera from dogs immunized with parvovirus are obtained, the polyclonal antibodies are purified and used to solve the high resolution cryo EM structures of the polyclonal Fab-virus complexes. We use a custom software, Icosahedral Subparticle Extraction and Correlated Classification (ISECC) to perform subparticle analysis and reconstruct polyclonal Fab-virus complexes from two different dogs eight and twelve weeks post vaccination. In the resulting polyclonal Fab-virus complexes there are a total of five distinct Fabs identified. In both cases, any of the five antibodies identified would interfere with receptor binding. This polyclonal mapping approach identifies a specific, limited immune response to the live vaccine virus and allows us to investigate the binding of multiple different antibodies or ligands to virus capsids.
Topics: Animals; Dogs; Parvovirus, Canine; Antibody Formation; Cryoelectron Microscopy; Antibodies; Vaccination
PubMed: 37726539
DOI: 10.1038/s42003-023-05319-7 -
Viruses May 2024Reports of newly discovered equine hepatotropic flavi- and parvoviruses have emerged throughout the last decade in many countries, the discovery of which has stimulated...
Reports of newly discovered equine hepatotropic flavi- and parvoviruses have emerged throughout the last decade in many countries, the discovery of which has stimulated a great deal of interest and clinical research. Although commonly detected in horses without signs of disease, equine parvovirus hepatitis (EqPV-H) and equine hepacivirus (EqHV) have been associated with liver disease, including following the administration of contaminated anti-toxin. Our aim was to determine whether EqPV-H and EqHV are present in Australian horses and whether EqPV-H was present in French horses and to examine sequence diversity between strains of both viruses amongst infected horses on either side of the globe. Sera from 188 Australian horses and 256 French horses from horses with and without clinical signs of disease were collected. Twelve out of 256 (4.7%) and 6 out of 188 (3.2%) French and Australian horses, respectively, were positive for the molecular detection of EqPV-H. Five out of 256 (1.9%) and 21 out of 188 (11.2%) French and Australian horses, respectively, were positive for the molecular detection of EqHV. Australian strains for both viruses were genomically clustered, in contrast to strains from French horses, which were more broadly distributed. The findings of this preliminary survey, with the molecular detection of EqHV and EqPV-H in Australia and the latter in France, adds to the growing body of awareness regarding these recently discovered hepatotropic viruses. It has provided valuable information not just in terms of geographic endemicity but will guide equine clinicians, carers, and authorities regarding infectious agents and potential impacts of allogenic tissue contamination. Although we have filled many gaps in the world map regarding equine hepatotropic viruses, further prospective studies in this emerging field may be useful in terms of elucidating risk factors and pathogenesis of these pathogens and management of cases in terms of prevention and diagnosis.
Topics: Animals; Horses; Horse Diseases; Australia; Parvoviridae Infections; Phylogeny; France; Hepatitis, Viral, Animal; Parvovirus; Hepacivirus; Hepatitis C
PubMed: 38932156
DOI: 10.3390/v16060862 -
Journal of Medical Virology Oct 2023In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a...
In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV-6) and 7 (HHV-7), parvovirus B19 (B19V), enterovirus (EV), Epstein-Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS-CoV-2. Differential diagnosis was carried out on 289 discarded cases by multiplex real-time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV-7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV-6, EV, HAdV, and HCMV-positive cases were found in children aged 0-4 years and HHV-7 was most frequent in the 15-39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus-positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities.
Topics: Child; Humans; Adolescent; Young Adult; Adult; Diagnosis, Differential; Epstein-Barr Virus Infections; Antibodies, Viral; Immunoglobulin M; Herpesvirus 4, Human; Measles; Rubella; Measles virus; Enterovirus; Exanthema; Fever; Enterovirus Infections; Herpesvirus 6, Human; Adenoviruses, Human
PubMed: 37796084
DOI: 10.1002/jmv.29141 -
Circulation. Genomic and Precision... Oct 2023Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to...
BACKGROUND
Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases.
METHODS
We performed whole exome and genome sequencing of 122 explanted hearts from 101 adult and 21 pediatric patients with idiopathic cardiomyopathy from a single center. Data were analyzed for pathogenic/likely pathogenic variants in nuclear and mitochondrial genomes and assessed for nonhuman microbial sequences. The frequency of damaging genetic variants was compared among cardiomyopathy cohorts with different clinical severity.
RESULTS
Fifty-four samples (44.3%) had pathogenic/likely pathogenic cardiomyopathy gene variants. The frequency of pathogenic variants was similar in pediatric (42.9%) and adult (43.6%) samples, but the distribution of mutated genes differed (=8.30×10). The prevalence of causal genetic variants was significantly higher in end-stage than in previously reported ambulatory adult dilated cardiomyopathy cases (<0.001). Among remaining samples with unexplained causes, no damaging mitochondrial variants were identified, but 28 samples contained parvovirus genome sequences, including 2 samples with 6- to 9-fold higher levels than the overall mean levels in other samples.
CONCLUSIONS
Pathogenic variants and viral myocarditis were identified in 45.9% of patients with unexplained end-stage cardiomyopathy. Damaging gene variants are significantly more frequent among transplant compared with patients with ambulatory cardiomyopathy. Genetic analyses can help define cause of end-stage cardiomyopathy to guide management and risk stratification of patients and family members.
Topics: Adult; Humans; Child; Cardiomyopathies; Cardiomyopathy, Dilated; Heart Transplantation; Heart Failure
PubMed: 37767697
DOI: 10.1161/CIRCGEN.123.004062 -
Seminars in Fetal & Neonatal Medicine Feb 2024Congenital infections are a common but often underrecognized cause of fetal brain abnormalities, as well as fetal-neonatal morbidity and mortality, that should be... (Review)
Review
Congenital infections are a common but often underrecognized cause of fetal brain abnormalities, as well as fetal-neonatal morbidity and mortality, that should be considered by all healthcare professionals providing neurological care to fetuses and newborns. Maternal infection with various pathogens (cytomegalovirus, Toxoplasmosis, Rubella virus, Parvovirus B19, lymphocytic choriomeningitis virus, syphilis, Zika virus, varicella zoster virus) during pregnancy can be transmitted to the developing fetus, which can cause multisystem dysfunction and destructive or malformative central nervous system lesions. These can be recognized on fetal and neonatal imaging, including ultrasound and MRI. Imaging and clinical features often overlap, but some distinguishing features can help identify specific pathogens and guide subsequent testing strategies. Some pathogens can be specifically treated, and others can be managed with targeted interventions or symptomatic therapy based on expected complications. Neurological and neurodevelopmental complications related to congenital infections vary widely and are likely driven by a combination of pathophysiologic factors, alone or in combination. These include direct invasion of the fetal central nervous system by pathogens, inflammation of the maternal-placental-fetal triad in response to infection, and long-term effects of immunogenic and epigenetic changes in the fetus in response to maternal-fetal infection. Congenital infections and their neurodevelopmental impacts should be seen as an issue of public health policy, given that infection and the associated complications disproportionately affect woman and children from low- and middle-income countries and those with lower socio-economic status in high-income countries. Congenital infections may be preventable and treatable, which can improve long-term neurodevelopmental outcomes in children.
Topics: Humans; Pregnancy; Female; Pregnancy Complications, Infectious; Infant, Newborn; Infectious Disease Transmission, Vertical; Brain Diseases
PubMed: 38677956
DOI: 10.1016/j.siny.2024.101526 -
Molecular Medicine Reports Oct 2023Human parvovirus B19 (B19V) has been strongly associated with a variety of inflammatory disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease and...
Human parvovirus B19 (B19V) has been strongly associated with a variety of inflammatory disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. Non‑structural protein 1 (NS1) of B19V has been demonstrated to play essential roles in the pathological processes of B19V infection due to its regulatory properties on inflammatory cytokines. Celastrol, a quinone methide isolated from , has displayed substantial potential in treating inflammatory diseases, such as psoriasis and RA. However, little is known about the effects of celastrol on B19V NS1‑induced inflammation. Therefore, cell viability assay, migration assay, phagocytosis analysis, zymography assay, ELISA and immunoblotting were conducted to verify the influences of celastrol on macrophages. The present study reported the attenuating effects of celastrol on B19V NS1‑induced inflammatory responses in macrophages derived from human acute monocytic leukemia cell lines, U937 and THP‑1. Although the migration was not significantly decreased by celastrol in both U937 and THP‑1 macrophages, significantly decreased viability, migration and phagocytosis were detected in both B19V NS1‑activated U937 and THP‑1 macrophages in the presence of celastrol. Additionally, celastrol significantly decreased MMP‑9 activity and the levels of inflammatory cytokines, including IL‑6, TNF‑α and IL‑1β, in B19V NS1‑activated U937 and THP‑1 cells. Notably, significantly decreased levels of NLR family pyrin domain‑containing 3, apoptosis‑associated speck‑like, caspase‑1 and IL‑18 proteins were observed in both B19V NS1‑activated U937 and THP‑1 cells in the presence of celastrol, indicating the involvement of the inflammasome pathway. To the best of our knowledge, the present study is the first to report on the attenuating effects of celastrol on B19V NS1‑induced inflammatory responses in macrophages, suggesting a therapeutic role for celastrol in B19V NS1‑related inflammatory diseases.
Topics: Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Parvovirus B19, Human; Macrophages; Arthritis, Rheumatoid; Cytokines
PubMed: 37654202
DOI: 10.3892/mmr.2023.13080 -
Medical Journal, Armed Forces India 2023Parvovirus B19 is an uncommon cause of anaemia in kidney transplant recipients (KTRs). The study aims to determine the incidence, clinical presentation, laboratory...
BACKGROUND
Parvovirus B19 is an uncommon cause of anaemia in kidney transplant recipients (KTRs). The study aims to determine the incidence, clinical presentation, laboratory findings and outcome of parvovirus B19-related anaemia in KTR.
METHOD
We conducted a 12-year retrospective, single-centre study describing the clinical profile of KTRs with parvovirus B19-related anaemia.
RESULT
Amongst the 714 patients who underwent kidney transplantation between January 2011 and January 2023, (cumulative follow-up: 1287 patient-years), six females and one male, developed parvovirus B19-related anaemia. The incidence proportion (risk) is 0.98% with an incidence rate of 5.43 cases per 1000 patient-year. The median duration from transplant to development of anaemia was 6 weeks (range: 4-40 weeks). The mean fall in haemoglobin was 2.88 ± 1.55 gm/dl; concomitant leukopenia and thrombocytopenia were observed in 57.1 and 28.6% of patients. Three patients responded to a reduction in immunosuppression, the four non-responders required the administration of low-dose intravenous immunoglobulin. The mean duration from initiation of therapy to a sustained rise in haemoglobin was 7.71 ± 2.62 weeks. None of the patients had a relapse of the infection.
CONCLUSIONS
Parvovirus B19 infection is an uncommon cause of post-transplant refractory anaemia. The key to successfully managing such patients includes a high index of suspicion, early diagnosis and reduction of immunosuppression with or without administration of intravenous immunoglobulin.
PubMed: 37981933
DOI: 10.1016/j.mjafi.2023.08.005 -
Journal of Biomolecular Structure &... 2023This article was aimed at analyzing the sequence, structure, and function of the two Muscovy duck parvovirus proteins, including REP and VP1. The antigenicity, physical...
This article was aimed at analyzing the sequence, structure, and function of the two Muscovy duck parvovirus proteins, including REP and VP1. The antigenicity, physical and chemical properties, transmembrane regions, phosphorylation sites, glycosylation sites, three-dimensional structure, and linear epitope of VP1 and REP were predicted and analyzed through bioinformatics methods. A multi-epitope vaccine was also constructed based on the screened epitopes, and the vaccine was characterized, modeled, molecularly docked and molecularly cloned. The epitopes were screened according to the criteria of antigenicity, non-allergenicity and non-toxicity, and 12 epitope fragments were obtained. The B cell epitopes were analyzed according to four scales: β-turn, hydrophilicity, surface accessibility and antigenicity. Combined with the epitope prediction results based on structure, the final epitope prediction results were obtained. The multi-epitope vaccine used an EAAAK-linked adjuvant, a GPGPG-linked T-cell epitope, and a KK-linked B-cell epitope. The analysis showed that the vaccine was stable hydrophilic, antigenic, conserved and non-allergenic. Based on molecular docking it was shown that good interactions between the vaccine and the immune receptor were generated and were essential to generate an immune response. The final vaccine was reverse translated into cDNA and the DNA vaccine was designed by codon optimization and molecular cloning. Further trials are still needed to demonstrate the immunogenicity and other aspects of vaccine efficacy.Communicated by Ramaswamy H. Sarma.
PubMed: 36065642
DOI: 10.1080/07391102.2022.2118170 -
Viruses Oct 2023Viral disinfection is important for medical facilities, the food industry, and the veterinary field, especially in terms of controlling virus outbreaks. Therefore,... (Review)
Review
Viral disinfection is important for medical facilities, the food industry, and the veterinary field, especially in terms of controlling virus outbreaks. Therefore, standardized methods and activity levels are available for these areas. Usually, disinfectants used in these areas are characterized by their activity against test organisms (i.e., viruses, bacteria, and/or yeasts). This activity is usually determined using a suspension test in which the test organism is incubated with the respective disinfectant in solution to assess its bactericidal, yeasticidal, or virucidal activity. In addition, carrier methods that more closely reflect real-world applications have been developed, in which microorganisms are applied to the surface of a carrier (e.g., stainless steel frosted glass, or polyvinyl chloride (PVC)) and then dried. However, to date, no standardized methods have become available for addressing genetically modified vectors or disinfection-resistant oncolytic viruses such as the H1-parvovirus. Particularly, such non-enveloped viruses, which are highly resistant to disinfectants, are not taken into account in European standards. This article proposes a new activity claim known as "virucidal activity PLUS", summarizes the available methods for evaluating the virucidal activity of chemical disinfectants against genetically modified organisms (GMOs) using current European standards, including the activity against highly resistant parvoviridae such as the adeno-associated virus (AAV), and provides guidance on the selection of disinfectants for pharmaceutical manufacturers, laboratories, and clinical users.
Topics: Humans; Disinfectants; Disinfection; Viruses; Parvovirus; Parvoviridae Infections
PubMed: 38005856
DOI: 10.3390/v15112179 -
Microbiology Spectrum Aug 2023DNA replication is a standard and essential function among DNA viruses; however, this functional domain's common ancestor, origin, and evolutionary path in invertebrate-...
DNA replication is a standard and essential function among DNA viruses; however, this functional domain's common ancestor, origin, and evolutionary path in invertebrate- and vertebrate-infecting viruses are not yet fully understood. Here, we present evidence, using a combination of phylogenetic relationships, coevolution, and CLANS (cluster analysis of sequences) analysis, that the parvo-NS1 domain (nonstructural protein NS1, DNA helicase domain) of these DNA viruses that infect vertebrates potentially originated from the invertebrate (Platyhelminthes) parvo-NS1 domain of parvovirus-related sequences (PRSs). Our results suggest that papillomaviruses and the parvovirus subfamilies and DNA helicase evolved directly from the Platyhelminthes NS1 domain (PRSs). Similarly, the parvovirus subfamily NS1 domain displayed evolutionary heritage from the PRSs through Further, our analysis also clarified that herpesviruses and adenoviruses independently obtained the parvo-NS1 domain from (). Furthermore, virus-host coevolution analysis revealed that the parvovirus NS1 domain has coevolved with hosts, from flatworms to humans, and it appears that the papillomavirus may have obtained the DNA helicase during the early stages of parvovirus evolution and later led to the development of the DNA helicase of adomavirus and polyomavirus. Finally, herpesviruses and adenoviruses likely inherited the parvo-NS1 domain from in the later stages of evolution. To the best of our knowledge, this is the first evolutionary evidence to suggest that the DNA helicase of viruses that infect vertebrates originated from the invertebrate PRSs. DNA replication of DNA viruses is an essential function. This allows DNA replication of viruses to form virus particles. The DNA helicase domain is responsible for this primary function. This domain is present in parvoviruses, papillomaviruses, polyomaviruses, herpesviruses, and adenoviruses. But little is known about the common ancestor, origin, and evolutionary path of DNA helicase in invertebrate- and vertebrate-infecting viruses. Here, we report the possibility of the origin of DNA viruses (DNA helicase) infecting vertebrates from Platyhelminthes (invertebrate) PRSs. Our study established that the parvovirus subfamily NS1 domain displayed evolutionary heritage from the Platyhelminthes PRSs through . Furthermore, our study suggests that the papillomavirus DNA helicase may have evolved in the early stages of parvovirus evolution and then led to the development of the adomavirus and polyomavirus. Our study suggests that the herpesviruses and adenoviruses likely inherited the parvo-NS1 domain through gene capture from in the later stages of parvovirus evolution in their hosts.
Topics: Animals; Humans; Phylogeny; DNA Viruses; Invertebrates; Parvovirus; Vertebrates; Parvoviridae Infections; Adenoviridae; DNA Helicases
PubMed: 37347193
DOI: 10.1128/spectrum.04570-22