-
Poultry Science Jun 2024Migratory wild birds can carry various pathogens, such as influenza A virus, which can spread to globally and cause disease outbreaks and epidemics. Continuous...
Migratory wild birds can carry various pathogens, such as influenza A virus, which can spread to globally and cause disease outbreaks and epidemics. Continuous epidemiological surveillance of migratory wild birds is of great significance for the early warning, prevention, and control of epidemics. To investigate the pathogen infection status of migratory wild birds in eastern China, fecal samples were collected from wetlands to conduct pathogen surveillance. The results showed that duck orthoreovirus (DRV) and goose parvovirus (GPV) nucleic acid were detected positive in the fecal samples collected from wild ducks, egrets, and swan. Phylogenetic analysis of the amplified viral genes reveals that the isolates were closely related to the prevalent strains in the regions involved in East Asian-Australasian (EAA) migratory flyway. Phylogenetic analysis of the amplified viral genes confirmed that they were closely related to circulating strains in the regions involved in the EAA migration pathway. The findings of this study have expanded the host range of the orthoreovirus and parvovirus, and revealed possible virus transmission between wild migratory birds and poultry.
PubMed: 38909506
DOI: 10.1016/j.psj.2024.103940 -
Euro Surveillance : Bulletin Europeen... Jun 2024From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher...
From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.
Topics: Humans; France; Parvovirus B19, Human; Disease Outbreaks; Adult; Female; Male; Child; Parvoviridae Infections; Immunoglobulin M; Adolescent; Child, Preschool; Middle Aged; Antibodies, Viral; Erythema Infectiosum; Young Adult; Infant; Aged
PubMed: 38904112
DOI: 10.2807/1560-7917.ES.2024.29.25.2400339 -
Journal of Veterinary Internal Medicine Jun 2024Equine parvovirus hepatitis (EqPV-H) can cause Theiler's disease and subclinical hepatitis in horses.
BACKGROUND
Equine parvovirus hepatitis (EqPV-H) can cause Theiler's disease and subclinical hepatitis in horses.
OBJECTIVES
Assess the frequency of subclinical EqPV-H infection in hospitalized horses and to study viral transmission by investigating potential shedding routes.
ANIMALS
One hundred sixteen equids, that presented to the University Equine Hospital of the University of Veterinary Medicine Vienna between February 2021 and March 2022, for causes other than hepatopathy.
METHODS
In this cross-sectional study, samples (serum, feces, nasal, and buccal swabs) of hospitalized horses were collected. Sera were screened for the presence of anti-EqPV-H antibodies by a luciferase immunoprecipitation system assay. Quantitative PCR was used for the detection of EqPV-H DNA in the samples and a nested PCR was used for further validation.
RESULTS
Seroprevalence was 10.3% (12/116) and viremia occurred in 12.9% (15/116) of the serologically positive horses. The detected viral load in serum varied from non-quantifiable amount to 1.3 × 10 genome equivalents per milliliter of serum. A low viral load of EqPV-H DNA was detected in 2 nasal swabs and 1 fecal sample.
CONCLUSION AND CLINICAL IMPORTANCE
EqPV-H DNA was detected in nasal secretions and feces of viremic horses, which could pose a risk to naive hospitalized horses. It is advisable to screen hospitalized horses that are potential donors of blood or plasma to reduce the risk of iatrogenic EqPV-H transmission.
PubMed: 38899610
DOI: 10.1111/jvim.17129 -
Applied Microbiology and Biotechnology Jun 2024Recombinant adeno-associated virus (rAAV) is a major gene delivery vehicle. We have constructed a stable rAAV producer cell line by integrating essential rAAV genome,... (Comparative Study)
Comparative Study
Recombinant adeno-associated virus (rAAV) is a major gene delivery vehicle. We have constructed a stable rAAV producer cell line by integrating essential rAAV genome, viral and helper genes into the genome of HEK293 cell under the control of inducible promoters. Upon induction, the cell line produces transducing rAAV. To gain insight into enhancing rAAV productivity and vector quality, we performed a comparative transcriptomic and proteomic analysis of our synthetic cell line GX2 and two wild-type AAV (wtAAV) production systems, one by virus co-infection and the other by multi-plasmid transfection. The three systems had different kinetics in viral component synthesis but generated comparable copies of AAV genomes; however, the capsid titer of GX2 was an order of magnitude lower compared to those two wtAAV systems, indicating that its capsid production may be insufficient. The genome packaging efficiency was also lower in GX2 despite it produced higher levels of Rep52 proteins than either wtAAV systems, suggesting that Rep52 protein expression may not limit genome packaging. In the two wtAAV systems, VP were the most abundant AAV proteins and their levels continued to increase, while GX2 had high level of wasteful cargo gene expression. Furthermore, upregulated inflammation, innate immune responses, and MAPK signaling, as well as downregulated mitochondrial functions, were commonly observed in either rAAV or wtAAV systems. Overall, this comparative multi-omics study provided rich insights into host cell and viral factors that are potential targets for genetic and process intervention to enhance the productivity of synthetic rAAV producer cell lines. KEY POINTS: • wtAAV infection was more efficient in producing full viral particles than the synthetic cell GX2. • Capsid protein synthesis, genome replication, and packaging may limit rAAV production in GX2. • wtAAV infection and rAAV production in GX2 elicited similar host cell responses.
Topics: Dependovirus; Humans; HEK293 Cells; Proteomics; Transcriptome; Genetic Vectors; Kinetics; Genome, Viral; Gene Expression Profiling; Proteome
PubMed: 38896252
DOI: 10.1007/s00253-024-13203-5 -
Translational Vision Science &... Jun 2024To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a...
PURPOSE
To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector.
DESIGN
Single-center, retrospective chart review.
METHODS
In this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated.
RESULTS
Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector.
CONCLUSIONS
We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes.
TRANSLATIONAL RELEVANCE
Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.
Topics: Humans; Retrospective Studies; Genetic Vectors; Genetic Therapy; Male; Female; Child; Visual Acuity; Tomography, Optical Coherence; cis-trans-Isomerases; Dependovirus; Atrophy; Visual Fields
PubMed: 38888288
DOI: 10.1167/tvst.13.6.11 -
PLoS Pathogens Jun 2024Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of...
Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of AAV variants is far from being understood, except that genetic recombination plays an important role. Furthermore, little is known about the interaction between AAV and its natural hosts, human and nonhuman primates. In this study, natural AAV capsid genes were subjected to systemic evolutionary analysis with a focus on selection drives during the diversification of AAV lineages. A number of positively selected sites were identified from these AAV lineages with functional relevance implied by their localization on the AAV structures. The selection drives of the two AAV2 capsid sites were further investigated in a series of biological experiments. These observations did not support the evolution of the site 410 of the AAV2 capsid driven by selection pressure from the human CD4+ T-cell response. However, positive selection on site 548 of the AAV2 capsid was directly related to host humoral immunity because of the profound effects of mutations at this site on the immune evasion of AAV variants from human neutralizing antibodies at both the individual and population levels. Overall, this work provides a novel interpretation of the genetic diversity and evolution of AAV lineages in their natural hosts, which may contribute to their further engineering and application in human gene therapy.
Topics: Dependovirus; Humans; Animals; Evolution, Molecular; Capsid Proteins; Selection, Genetic; Genetic Variation; Genetic Therapy
PubMed: 38885242
DOI: 10.1371/journal.ppat.1012260 -
Research Square Jun 2024Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus,...
Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain. BMRB submission code: 52440.
PubMed: 38883784
DOI: 10.21203/rs.3.rs-4441481/v1 -
Infectious Diseases in Obstetrics and... 2024Transplacental infections are frequent, especially in developing countries, where limited screening is performed to find infectious agents in the pregnant population. We...
INTRODUCTION
Transplacental infections are frequent, especially in developing countries, where limited screening is performed to find infectious agents in the pregnant population. We aim to determine the clinical and epidemiological characteristics and seroinfection of antibodies against , parvovirus B19, , and HIV in pregnant women who attended the Motupe Health Center in Lambayeque, Peru during July-August 2018.
METHODS
A descriptive cross-sectional study was conducted in 179 pregnant women interviewed with a standardized questionnaire. ELISA was used to determine antibodies to and parvovirus B19. The detection of syphilis and HIV was conducted using immunochromatography, while the detection of hepatitis B was conducted using FTA-ABS and immunofluorescence, respectively.
RESULTS
Of 179 pregnant women, syphilis and HIV infections routinely included in the screening of pregnant women presented a seroinfection of 2.2 and 0.6%, respectively. Toxoplasmosis seroinfection was 25.1%, while IgM antiparvovirus B19 was 40.8%, revealing that pregnant women had an active infection at the time of study.
CONCLUSION
The level of seroinfection of toxoplasmosis reveals the risk to which pregnant women who participated in the study are exposed. The high seroinfection of parvovirus B19 could explain the cases of spontaneous abortion and levels of anemia in newborn that have been reported in Motupe, Lambayeque, Peru. However, future causality studies are necessary to determine the significance of these findings.
Topics: Humans; Female; Pregnancy; Peru; Treponema pallidum; Adult; Cross-Sectional Studies; Syphilis; Pregnancy Complications, Infectious; Toxoplasmosis; HIV Infections; Toxoplasma; Young Adult; Parvovirus B19, Human; Antibodies, Protozoan; Antibodies, Viral; Adolescent; Seroepidemiologic Studies
PubMed: 38883209
DOI: 10.1155/2024/8844325 -
Proceedings of the National Academy of... Jun 2024Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5...
Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5 kb that encodes a small noncoding RNA of 140 nucleotides known as bocavirus-encoded small RNA (BocaSR), in addition to viral proteins. Here, we determined the secondary structure of BocaSR in vivo by using DMS-MaPseq. Our findings reveal that BocaSR undergoes N6-methyladenosine (m6A) modification at multiple sites, which is critical for viral DNA replication in both dividing HEK293 cells and nondividing cells of the human airway epithelium. Mechanistically, we found that m6A-modified BocaSR serves as a mediator for recruiting Y-family DNA repair DNA polymerase (Pol) η and Pol κ likely through a direct interaction between BocaSR and the viral DNA replication origin at the right terminus of the viral genome. Thus, this report represents direct involvement of a viral small noncoding RNA in viral DNA replication through m6A modification.
Topics: Humans; Adenosine; Virus Replication; DNA-Directed DNA Polymerase; DNA Replication; DNA, Viral; HEK293 Cells; RNA, Viral; Human bocavirus; Genome, Viral; Parvoviridae Infections
PubMed: 38875150
DOI: 10.1073/pnas.2320782121 -
Euro Surveillance : Bulletin Europeen... Jun 2024We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent...
We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.
Topics: Humans; Female; Pregnancy; Denmark; Parvovirus B19, Human; Pregnancy Complications, Infectious; Adult; Incidence; Parvoviridae Infections; Epidemics; Hydrops Fetalis; Severity of Illness Index; Young Adult; Erythema Infectiosum; Adolescent; Abortion, Spontaneous; Population Surveillance
PubMed: 38873795
DOI: 10.2807/1560-7917.ES.2024.29.24.2400299