-
Infection, Genetics and Evolution :... Sep 2019Detection of infectious viral agents has been on the increase globally with the advent and usage of more sensitive and selective novel molecular techniques in the... (Review)
Review
Detection of infectious viral agents has been on the increase globally with the advent and usage of more sensitive and selective novel molecular techniques in the epidemiological study of viral diseases of economic importance to the swine industry. The observation is not different for the pig-infecting member of the subfamily Parvovirinae in the family Parvoviridae as the application of novel molecular methods like metagenomics has brought about the detection of many other novel members of the group. Surprisingly, the list keeps increasing day by day with some of them possessing zoonotic potentials. In the last one decade, not less than ten novel swine-infecting viruses have been added to the subfamily, and ceaseless efforts have been in top gear to determine the occurrence and prevalence of the old and new swine parvoviruses in herds of pig-producing countries worldwide. The story, however, is on the contrary on the African continent as there is presently a dearth of information on surveillance initiatives of the viruses among swine herds of pig-producing countries in the region. Timely detection and characterization of the viral pathogens is highly imperative for the implementation of effective control and prevention of its spread. This review therefore presents a concise overview on the epidemiology of novel porcine parvoviruses globally and also provides up-to-date highlights on the reported cases of the viral agents in the African sub-region.
Topics: Africa; Animals; Parvoviridae Infections; Parvovirus; Swine; Swine Diseases
PubMed: 31048075
DOI: 10.1016/j.meegid.2019.04.029 -
European Journal of Pharmaceutics and... Aug 2023Development and manufacturing adeno-associated virus (AAV)-based vectors for gene therapy requires suitable analytical methods to assess the quality of the formulations...
Development and manufacturing adeno-associated virus (AAV)-based vectors for gene therapy requires suitable analytical methods to assess the quality of the formulations during development, as well as the quality of different batches and the consistency of the processes. Here, we compare biophysical methods to characterize purity and DNA content of viral capsids from five different serotypes (AAV2, AAV5, AAV6, AAV8, and AAV9). For this purpose, we apply multiwavelength sedimentation velocity analytical ultracentrifugation (SV-AUC) to obtain the species' contents and to derive the wavelength-specific correction factors for the respective insert-size. In an orthogonal manner we perform anion exchange chromatography (AEX) and UV-spectroscopy and the three methods yield comparable results on empty/filled capsid contents with these correction factors. Whereas AEX and UV-spectroscopy can quantify empty and filled AAVs, only SV-AUC could identify the low amounts of partially filled capsids present in the samples used in this study. Finally, we employ negative-staining transmission electron microscopy and mass photometry to support the empty/filled ratios with methods that classify individual capsids. The obtained ratios are consistent throughout the orthogonal approaches as long as no other impurities and aggregates are present. Our results show that the combination of selected orthogonal methods can deliver consistent empty/filled contents on non-standard genome sizes, as well as information on other relevant critical quality attributes, such as AAV capsid concentration, genome concentration, insert size length and sample purity to characterize and compare AAV preparations.
Topics: Capsid; Dependovirus; Genetic Vectors; Capsid Proteins; Ultracentrifugation; DNA
PubMed: 37196871
DOI: 10.1016/j.ejpb.2023.05.011 -
Frontiers in Immunology 2021Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing β-cells and hyperglycaemia. Much of the knowledge about... (Review)
Review
Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing β-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering β-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mechanisms that lead to virus-induced T1D. Both animals develop β-cell inflammation and hyperglycemia upon infection with the parvovirus Kilham Rat Virus (KRV). Our earlier and studies indicated that KRV-induced innate immune upregulation early in the disease course plays a causal role in triggering β-cell inflammation and destruction. Furthermore, we recently found for the first time that infection with KRV induces inflammation in visceral adipose tissue (VAT) detectable as early as day 1 post-infection prior to insulitis and hyperglycemia. The proinflammatory response in VAT is associated with macrophage recruitment, proinflammatory cytokine and chemokine upregulation, endoplasmic reticulum (ER) and oxidative stress responses, apoptosis, and downregulation of adipokines and molecules that mediate insulin signaling. Downregulation of inflammation suppresses VAT inflammation and T1D development. These observations are strikingly reminiscent of data from obesity and type 2 diabetes (T2D) in which VAT inflammation is believed to play a causal role in disease mechanisms. We propose that VAT inflammation and dysfunction may be linked with the mechanism of T1D progression.
Topics: Animals; Diabetes Mellitus, Type 1; Humans; Intra-Abdominal Fat; Parvoviridae Infections; Parvovirus; Rats
PubMed: 34421908
DOI: 10.3389/fimmu.2021.702506 -
Frontiers in Immunology 2019Cancer cells utilize multiple mechanisms to evade and suppress anticancer immune responses creating a "cold" immunosuppressive tumor microenvironment. Oncolytic... (Review)
Review
Cancer cells utilize multiple mechanisms to evade and suppress anticancer immune responses creating a "cold" immunosuppressive tumor microenvironment. Oncolytic virotherapy is emerging as a promising approach to revert tumor immunosuppression and enhance the efficacy of other forms of immunotherapy. Growing evidence indicates that oncolytic viruses (OVs) act in a multimodal fashion, inducing immunogenic cell death and thereby eliciting robust anticancer immune responses. In this review, we summarize information about OV-mediated immune conversion of the tumor microenvironment. As a case study we focus on the rodent protoparvovirus H-1PV and its dual role as an oncolytic and immune modulatory agent. Potential strategies to improve H-1PV anticancer efficacy are also discussed.
Topics: H-1 parvovirus; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 31440242
DOI: 10.3389/fimmu.2019.01848 -
Journal of Veterinary Diagnostic... Jan 2021A juvenile raccoon was euthanized because of severe neurologic signs. At postmortem examination, no significant gross lesions were present. Histologic evaluation...
A juvenile raccoon was euthanized because of severe neurologic signs. At postmortem examination, no significant gross lesions were present. Histologic evaluation demonstrated nonsuppurative encephalitis in thalamus, brainstem, and hippocampus, cerebellar Purkinje cell loss, as well as poliomyelitis and demyelination of the spinal cord. Parvovirus antigen-specific immunohistochemistry revealed immunopositive neurons in the brainstem, cerebral cortex, and hippocampus. A few Purkinje cells were also immunopositive. DNA extracted from formalin-fixed, paraffin-embedded brain tissue (thalamus, hippocampus, cerebral cortex) yielded a positive signal using PCR targeting both feline and canine parvovirus. Sequencing analyses from a fragment of the NS1 gene and a portion of the VP2 gene confirmed the presence of DNA of a recent canine parvovirus variant (CPV-2a-like virus) in the cerebellum. Our case provides evidence that a recent canine parvovirus (CPV) strain () can infect cerebral and diencephalic neurons and cause encephalitis in an otherwise healthy raccoon. Parvovirus-induced encephalitis is a differential diagnosis of rabies and canine distemper in raccoons with neurologic signs.
Topics: Animals; Animals, Wild; Cerebellum; Encephalitis; Male; Minnesota; Parvoviridae Infections; Parvovirus, Canine; Raccoons
PubMed: 33100176
DOI: 10.1177/1040638720967381 -
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 -
GigaScience Dec 2022With the development of viral metagenomics and next-generation sequencing technology, more and more novel parvoviruses have been identified in recent years, including...
With the development of viral metagenomics and next-generation sequencing technology, more and more novel parvoviruses have been identified in recent years, including even entirely new lineages. The Parvoviridae family includes a different group of viruses that can infect a wide variety of animals. In this study, systematic analysis was performed to identify the "dark matter" (datasets that cannot be easily attributed to known viruses) of parvoviruses and to explore their genetic diversity from wild birds' cloacal swab samples. We have tentatively defined this parvovirus "dark matter" as a highly divergent lineage in the Parvoviridae family. All parvoviruses showed several characteristics, including 2 major protein-coding genes and similar genome lengths. Moreover, we observed that the novel parvo-like viruses share similar genome organizations to most viruses in Parvoviridae but could not clustered with the established subfamilies in phylogenetic analysis. We also found some new members associated with the Bidnaviridae family, which may be derived from parvovirus. This suggests that systematic analysis of domestic and wild animal samples is necessary to explore the genetic diversity of parvoviruses and to mine for more of this potential dark matter.
Topics: Animals; Animals, Wild; Phylogeny; Cloaca; Parvovirus; Parvoviridae Infections; Birds; High-Throughput Nucleotide Sequencing
PubMed: 36734170
DOI: 10.1093/gigascience/giad001 -
Transboundary and Emerging Diseases Sep 2022We conducted an exploratory serological survey to evaluate the exposure of Bornean wild carnivores to several viruses common to domestic felids, at interface areas...
We conducted an exploratory serological survey to evaluate the exposure of Bornean wild carnivores to several viruses common to domestic felids, at interface areas between protected forest and industrial agriculture in the Kinabatangan floodplain (Sabah, Malaysia). Blood samples, collected from wild carnivores (n = 21) and domestic cats (n = 27), were tested for antibodies against feline coronavirus (FCoV), feline panleukopenia virus (FPLV), feline herpesvirus (FHV) and feline calicivirus (FCV), using commercial enzyme-linked immunosorbent assay (ELISA) test kits. Anti-FCoV antibodies were detected in most species, including one flat-headed cat (Prionailurus planiceps, [1/2]), leopard cats (Prionailurus bengalensis, [2/5]), Malay civets (Viverra tangalunga, [2/11]) and domestic cats (Felis catus, [2/27]). Anti-FCV antibodies were present in all domestic cats and one flat-headed cat, while anti-FPLV antibodies were identified in Sunda clouded leopards (Neofelis diardi, [2/2]), domestic cats [12/27] and Malay civets [2/11]. Anti-FHV antibodies were only detected in domestic cats [2/27]. Our findings indicate pathogen transmission risk between domestic and wild carnivore populations at the domestic animal-wildlife interface, emphasizing the concern for wildlife conservation for several endangered wild carnivores living in the area. Special consideration should be given to species that benefit from their association with humans and have the potential to carry pathogens between forest and plantations (e.g., Malay civets and leopard cats). Risk reduction strategies should be incorporated and supported as part of conservation actions in human-dominated landscapes.
Topics: Animals; Animals, Domestic; Animals, Wild; Antibodies, Viral; Carnivora; Cat Diseases; Cats; Felidae; Feline Panleukopenia Virus; Humans; Viverridae
PubMed: 35373926
DOI: 10.1111/tbed.14549 -
Viruses Sep 2019Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have... (Review)
Review
Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens.
Topics: Animal Diseases; Animals; Cats; Diarrhea; Enterovirus Infections; Gastroenteritis; Kobuvirus; Norovirus; Parvovirus; Phylogeny; Viruses
PubMed: 31575055
DOI: 10.3390/v11100908 -
Journal of Pharmaceutical and... Sep 2023After more than two decades of research and development, adeno-associated virus (AAV) has become one of the dominant delivery vectors in gene therapy. Despite the...
After more than two decades of research and development, adeno-associated virus (AAV) has become one of the dominant delivery vectors in gene therapy. Despite the focused research, the cell entry pathway for AAV is still not fully understood. Universal AAV receptor (AAVR) has been identified to be involved in cellular entry of different AAV serotypes. With the unveiling of the high-resolution AAV-AAVR complex structure by cryogenic electron microscopy, the atomic level interaction between AAV and AAVR has become the focus of study in recent years. However, the serotype dependence of this binding interaction and the effect of pH have not been studied. Here, orthogonal approaches including bio-layer interferometry (BLI), size-exclusion chromatography coupled to multi-angle laser scattering (SEC-MALS) and sedimentation velocity analytical ultracentrifugation (SV-AUC) were utilized to study the interaction between selected AAV serotypes and AAVR under different pH conditions. A robust BLI method was developed and the equilibrium dissociation binding constants (K) between different AAV serotypes (AAV1, AAV5 and AAV8) and AAVR was measured. The binding constants measured by BLI together with orthogonal methods (SEC-MALS and SV-AUC) all confirmed that AAV5 has the strongest binding affinity followed by AAV1 while AAV8 binds the weakest. It was also observed that lower pH promotes the binding between AAV and AAVR and neutral or slightly basic conditions lead to very weak binding. These data indicate that for certain serotypes, AAVR may play a prominent role in trafficking AAV to the Golgi rather than acting as a host cell receptor. Information obtained from these combinatorial biophysical methods can be used to engineer future generations of AAVs to have better transduction efficiency.
Topics: Dependovirus; Hydrogen-Ion Concentration; Protein Binding; Serogroup
PubMed: 37441888
DOI: 10.1016/j.jpba.2023.115562