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Journal of Virology Oct 2023AAVs are extensively studied as promising therapeutic gene delivery vectors. In order to circumvent pre-existing antibodies targeting primate-based AAV capsids, the AAAV...
AAVs are extensively studied as promising therapeutic gene delivery vectors. In order to circumvent pre-existing antibodies targeting primate-based AAV capsids, the AAAV capsid was evaluated as an alternative to primate-based therapeutic vectors. Despite the high sequence diversity, the AAAV capsid was found to bind to a common glycan receptor, terminal galactose, which is also utilized by other AAVs already being utilized in gene therapy trials. However, contrary to the initial hypothesis, AAAV was recognized by approximately 30% of human sera tested. Structural and sequence comparisons point to conserved epitopes in the fivefold region of the capsid as the reason determinant for the observed cross-reactivity.
Topics: Animals; Humans; Capsid; Capsid Proteins; Dependovirus; Genetic Vectors; Primates; Antigens, Viral; Parvovirinae
PubMed: 37702486
DOI: 10.1128/jvi.00780-23 -
Clinical Immunology (Orlando, Fla.) Oct 2023High carrier prevalence of STAT3 SH2 domain somatic mutations was recently discovered in CD8+ T cells. We found these low-allele-fraction clones in 26% of donors,...
High carrier prevalence of STAT3 SH2 domain somatic mutations was recently discovered in CD8+ T cells. We found these low-allele-fraction clones in 26% of donors, without difference between multiple sclerosis (MS) patients and controls. Here we tested whether anti-viral antibodies associate with the carriership of these mutant clones. We compared antibody responses against common viruses in mutation carriers vs. non-carriers. Plasma samples of 152 donors (92 MS patients, 60 controls) were analyzed for antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6A and parvovirus B19. The mutation carrier status associated with EBV VCA IgG level (p = 0.005) and remained significant after logistic regression (p = 0.036). This association was contributed similarly by MS patients and controls. These results suggest that EBV contributes to the generation or growth of these clones. The pathogenic role of the STAT3 mutant clones in MS is presently unclear, but their detailed characterization warrants further study.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Capsid; src Homology Domains; Multiple Sclerosis; Antigens, Viral; Antibodies, Viral; Immunoglobulin G; CD8-Positive T-Lymphocytes; STAT3 Transcription Factor
PubMed: 37572949
DOI: 10.1016/j.clim.2023.109733 -
Microbiology Spectrum Aug 2023Porcine circovirus type 2 (PCV2) is an important swine infectious pathogen that seriously threatens the global swine industry. PCV2 Cap protein is the only structural...
Porcine circovirus type 2 (PCV2) is an important swine infectious pathogen that seriously threatens the global swine industry. PCV2 Cap protein is the only structural and the main immunogenic protein constituting the viral capsid. In this study, a gold nanoparticle-based immunochromatographic strip with high sensitivity and specificity was developed which could be used for rapid detection of PCV2 virions or Cap protein in research. The visual detection limit of the strip was 10 50% tissue culture infective does (TCID)/mL for PCV2, and 2.03 μg/mL for PCV2 Cap protein. No cross-reactivity was observed with the PCV1 and PCV3 Cap proteins and other common swine pathogens such as porcine reproductive and respiratory syndrome virus, classical swine fever virus, pseudorabies virus, porcine epidemic diarrhea virus, porcine parvovirus, and swine influenza virus. The repeatability of the strip was good. The stability of the strip was perfect for 12 months in a dry state at room temperature. Visual results could be obtained within 5 min by simply inserting the strip into the diluted sample. The strip is a time-saving, labor-saving, and reliable tool for testing of PCV2 virions or Cap protein in research. The idea of this study might open a new perspective for the application of the strip. Porcine circovirus type 2 (PCV2) Cap protein is the only structural and the main immunogenic protein constituting the viral capsid. Although many methods can be used to identify PCV2 or PCV2 Cap protein in vaccine research, they usually require high workload and time. The developed strip can specifically detect PCV2 virions or Cap protein, and visual qualitative results can be obtained within 5 min by simply diluting the sample and inserting the strip into the sample. The final value of the strip is providing a simple and time-saving method for real-time monitoring of PCV2 antigen in vaccine research with reliable results, such as the different stages of PCV2 Cap protein expression and purification, as well as the different stages of PCV2 reproduction and purification.
Topics: Animals; Swine; Circovirus; Gold; Swine Diseases; Circoviridae Infections; Metal Nanoparticles; Vaccines; Antibodies, Viral
PubMed: 37466437
DOI: 10.1128/spectrum.01953-22 -
Journal of Hematopathology Dec 2023A teenage girl presented with fevers of unknown origin and pancytopenia. Complete blood count showed anemia (hemoglobin, 9.0 g/dL), neutropenia (1.7 × 10/L), and...
A teenage girl presented with fevers of unknown origin and pancytopenia. Complete blood count showed anemia (hemoglobin, 9.0 g/dL), neutropenia (1.7 × 10/L), and thrombocytopenia (66 × 10/L). The bone marrow was hypocellular with left shifted hematopoiesis and myeloid hypoplasia. Aspirate smears were notable for a prominent population of neutrophils with crescentic nuclei that engulfed blue amorphous material (Fig. 1 panels A and B, Wright-Giemsa, magnification × 1000). The trephine biopsy showed similar cells with crescentic nuclei and eosinophilic material (Fig. 1 panels C and D, hematoxylin and eosin × 400). Flow cytometry was negative for an abnormal population. EBV by in situ hybridization and parvovirus immunohistochemistry were negative. Subsequent serologic testing was positive for ANA (1:1280), low C3/C4, anti-dsDNA, anti-SM and anti-B2GP1. A kidney biopsy demonstrated findings consistent with class III lupus nephritis.
Topics: Female; Adolescent; Humans; Neutrophils; Bone Marrow; Pancytopenia; Biopsy; Neutropenia
PubMed: 38175431
DOI: 10.1007/s12308-023-00561-8 -
The Science of the Total Environment Jun 2024For canine parvovirus -2 (CPV-2), a zoonotic virus capable of cross-species transmission in animals, the amino acid changes of capsid protein VP2 are key factors when...
For canine parvovirus -2 (CPV-2), a zoonotic virus capable of cross-species transmission in animals, the amino acid changes of capsid protein VP2 are key factors when binding to other species' transferrin receptors (TfR). CPV-2 variants can spread from felines and canines, for example, to Carnivora, Artiodactyla, and Pholidota species, and CPV-2c variants are essential to spread from Carnivora to Artiodactyla and Pholidota species in particular. In our study, a CPV-2a variant maintained a relatively stable trend, and the proportion of CPV-2c gradually rose from 1980 to 2021. The VP2 amino acid sequence analysis showed that five amino acid mutations at 426E/D, 305H/D, and 297S may be necessary for the virus to bind to different host receptors. Meanwhile, receptor-binding loop regions and amino acid sites 87 L, 93 N, 232I, and 305Y were associated with CPV-2 cross-species transmission. The homology of TfRs in different hosts infected with CPV-2 ranged from 77.2 % to 99.0 %, and from pig to feline, canine, and humans was 80.7 %, 80.4 %, and 77.2 %, respectively. The amino acid residues of TfRs involved in the viral binding in those hosts are highly conserved, which suggests that CPV-2 may be capable of pig-to-human transmission. Our analysis of the origin, evolutionary trend, cross-species transmission dynamics, and genetic characteristics of CPV-2 when binding to host receptors provides a theoretical basis for further research on CPV-2's mechanism of cross-species transmission and for establishing an early warning and monitoring mechanism for the possible threat of CPV-2 to animal-human public security.
Topics: Parvovirus, Canine; Animals; Dogs; Humans; Parvoviridae Infections; Cats; Capsid Proteins; Zoonoses; Receptors, Transferrin
PubMed: 38599392
DOI: 10.1016/j.scitotenv.2024.172307 -
Viruses Mar 2024This study presents an analysis of the epidemiological trends of parvovirus B19 (B19V) in Israel from 2010 to 2023, with particular emphasis on the outbreak in 2023. The...
This study presents an analysis of the epidemiological trends of parvovirus B19 (B19V) in Israel from 2010 to 2023, with particular emphasis on the outbreak in 2023. The analysis utilized molecular diagnostic data from individual patients obtained at the Central Virology Laboratory. Between 2010 and 2022, 8.5% of PCR-tested samples were positive for B19V, whereas in 2023, this percentage surged to 31% of PCR-tested samples. Throughout the study period, annual cycles consistently peaked in early spring/summer, with the most recent prominent outbreak occurring in 2016. Predominantly, diagnoses were made in children and women aged 20-39. Despite the notable surge in 2023, over 80% of positive cases continued to be observed in children and young women, with a decrease in cases during winter months. Furthermore, genotype 1a of the virus remained the predominant strain circulating during the outbreak. In light of these circumstances, consideration should be given to implementing screening measures, particularly among high-risk groups such as pregnant women.
Topics: Child; Humans; Female; Pregnancy; Parvovirus B19, Human; Parvoviridae Infections; Retrospective Studies; Israel; Disease Outbreaks; DNA, Viral; Antibodies, Viral
PubMed: 38543845
DOI: 10.3390/v16030480 -
Analytical Biochemistry Aug 2023Nucleic acids detection has become essential in the identification of many infectious diseases and tumors. Conventional qPCR instruments are not suitable for...
Nucleic acids detection has become essential in the identification of many infectious diseases and tumors. Conventional qPCR instruments are not suitable for point-of-care Moreover, current miniaturized nucleic acid detection equipment has limited throughput and multiplex detection capabilities, typically allowing the detection of a limited number of samples. Here, we present an affordable, portable, and high-throughput nucleic acid detection device for point-of-care detection. This portable device is approximately 220 × 165 × 140 mm in size and about 3 kg in weight. It can provide stable and accurate temperature control and analyze two fluorescent signals (FAM and VIC) and run 16 samples simultaneously. As a proof of concept, we used the two purified DNA samples from Bordetella pertussis and Canine parvovirus and the results showed good linearity and coefficient of variation. Moreover, this portable device can detect as low as 10 copies and has good specificity. Therefore, our device can provide advantages in real-time diagnosis of high-throughput nucleic acid detection in the field, especially for resource-limited conditions.
Topics: Real-Time Polymerase Chain Reaction; Point-of-Care Testing; Point-of-Care Systems; DNA; Nucleic Acid Amplification Techniques; Sensitivity and Specificity
PubMed: 37302776
DOI: 10.1016/j.ab.2023.115200 -
Pathogens (Basel, Switzerland) Aug 2023Virus-like particles (VLPs) comprise one or many structural components of virions, except their genetic material. Thus, VLPs keep their structural properties of cellular... (Review)
Review
Virus-like particles (VLPs) comprise one or many structural components of virions, except their genetic material. Thus, VLPs keep their structural properties of cellular recognition while being non-infectious. VLPs of Parvovirus B19 (B19V) can be produced by the heterologous expression of their structural proteins VP1 and VP2 in bacteria. These proteins are purified under denaturing conditions, refolded, and assembled into VLPs. Moreover, chimeric forms of VP2 have been constructed to harbor peptides or functional proteins on the surface of the particles without dropping their competence to form VLPs, serving as presenting nanoparticles. The in-vitro assembly approach offers exciting possibilities for the composition of VLPs, as more than one chimeric form of VP2 can be included in the assembly stage, producing multifunctional VLPs. Here, the heterologous expression and in-vitro assembly of B19V structural proteins and their chimeras are reviewed. Considerations for the engineering of the structural proteins of B19V are also discussed. Finally, the construction of multifunctional VLPs and their future potential as innovative medical tools are examined.
PubMed: 37623967
DOI: 10.3390/pathogens12081007 -
Avian Pathology : Journal of the W.V.P.A Jun 2024Intestinal dilatation syndrome (IDS) is a segmental enteropathy characterized by dilatation of the junction of the ileum and jejunum (Meckel's diverticulum). IDS...
Intestinal dilatation syndrome (IDS) is a segmental enteropathy characterized by dilatation of the junction of the ileum and jejunum (Meckel's diverticulum). IDS severely affects the poultry industry by causing a chronic and irreversible drop in egg laying, reducing feed conversion efficiency, and increasing the mortality rate. The clinical and pathological features of IDS in white laying hens were described, and viral molecular and metagenomic research was conducted. The 50- to 60-day-old chickens presented pale mucosa, apathy, depression, ruffled feathers, and diarrhoea, accompanied by a 20% loss in fertile egg production, 20% culling of birds, and 5% mortality. The main findings at necropsy were marked intestinal dilatation with intestinal stasis, a narrow distal jejunum in the region of Meckel's diverticulum, and undigested food. Microscopic analysis revealed marked atrophic lymphoplasmacytic and heterophilic enteritis with hyperplastic crypts, ulceration, and heterophilic and lymphoplasmacytic perineuritis. The molecular assays consistently detected the presence of chicken parvovirus in the three segments of the intestine, pancreas, and proventriculus, as well as chicken megrivirus in the intestinal contents. Marked atrophic enteritis with perineuritis and intestinal stasis are associated with clinical manifestations of poor intestinal absorption and secondary bacterial infection. Our data provide useful information about IDS and highlight the importance of further studies to determine the specific role of each detected virus in this syndrome.RESEARCH HIGHLIGHTS IDS presented pathognomonic dilatation of the jejunum up to Meckel's diverticulum.IDS caused weight loss, decreased egg production, and increased culling and mortality.Chicken parvovirus (ChPV) was consistently detected through PCR assays.Chicken megrivirus (ChMV) was consistently detected through viral metagenomics.
PubMed: 38916258
DOI: 10.1080/03079457.2024.2372486 -
Scientific Reports Sep 2023To understand the epidemiological and genetic characteristics of B19V, a multiple-province surveillance of patients with febrile rash illnesses (FRIs) were conducted in...
To understand the epidemiological and genetic characteristics of B19V, a multiple-province surveillance of patients with febrile rash illnesses (FRIs) were conducted in China during 2009 ~ 2021. The clinical specimens of 3,820 FRI patients were collected and tested for B19V DNA. A total of 99 (2.59%) patients were positive for B19V, and 49 (49.49%) were children under 5 years old. B19V infections occurred throughout the year without obvious seasonal pattern. Ten NS1-VP1u sequences and seven genome sequences were obtained in this study, identified as subgenotype 1a. Combined with the globally representative genome sequences, no temporal and geographic clustering trends of B19V were observed, and there was no significant correlation between B19V sequences and clinical manifestations. The evolutionary rate of the B19V genome was 2.30 × 10 substitutions/site/year. The number of negative selection sites was higher than that of positive selection sites. It was the first to comprehensively describe the prevalence patterns and evolutionary characteristics of B19V in FRI patients in China. B19V played the role in FRI patients. Children under 5 years old were the main population of B19V infection. Subgenotype 1a was prevalent in FRI patients in China. B19V showed a high mutation rate, while negative selection acted on the genome.
Topics: Child; Humans; Child, Preschool; Parvovirus B19, Human; China; Exanthema; Acceptance and Commitment Therapy; Biological Evolution
PubMed: 37741897
DOI: 10.1038/s41598-023-43158-y