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Viruses Mar 2022Idiopathic chronic diarrhea (ICD) is a little understood common clinical problem in captive rhesus macaques claiming 33% of medical culls unrelated to research. The...
Idiopathic chronic diarrhea (ICD) is a little understood common clinical problem in captive rhesus macaques claiming 33% of medical culls unrelated to research. The eukaryotic virome in digestive tract tissues collected at necropsy from nine animals with ICD was characterized using viral metagenomics. We compared the distribution of viral reads in tissues and mucosal scrapings from the stomach, duodenum, jejunum, ileum, and the proximal, transverse, and distal colons. In situ hybridization (ISH) using viral probes were performed on fixed tissues. Deep sequencing revealed multiple viruses in the and family. Tissues and mucosal scraping from the same locations showed closely related viral reads contents while different gut tissues from the same animal varied widely. ISH showed punctuated staining for both RNA and DNA viruses in the distal colon. Parvovirus staining was also detected in the stomach/duodenum/jejunum in distinct oval-shaped structures. The location of enteric viral nucleic acid differed widely between different viral families and along the length of the digestive tract.
Topics: Animals; Diarrhea; Feces; Humans; Ileum; Macaca mulatta; Metagenomics; Nucleic Acids; Parvovirus; Viruses
PubMed: 35337045
DOI: 10.3390/v14030638 -
Journal of Virology Jul 2018Antibody and receptor binding are key virus-host interactions that control host range and determine the success of infection. Canine and feline parvovirus capsids bind...
Antibody and receptor binding are key virus-host interactions that control host range and determine the success of infection. Canine and feline parvovirus capsids bind the transferrin receptor type 1 (TfR) to enter host cells, and specific structural interactions appear necessary to prepare the stable capsids for infection. Here, we define the details of binding, competition, and occupancy of wild-type and mutant parvovirus capsids with purified receptors and antibodies. TfR-capsid binding interactions depended on the TfR species and varied widely, with no direct relationship between binding affinity and infection. Capsids bound feline, raccoon, and black-backed jackal TfRs at high affinity but barely bound canine TfRs, which mediated infection efficiently. TfRs from different species also occupied capsids to different levels, with an estimated 1 to 2 feline TfRs but 12 black-backed jackal TfRs binding each capsid. Multiple alanine substitutions within loop 1 on the capsid surface reduced TfR binding but substitutions within loop 3 did not, suggesting that loop 1 directly engaged the TfR and loop 3 sterically affected that interaction. Binding and competition between different TfRs and/or antibodies showed complex relationships. Both antibodies 14 and E competed capsids off TfRs, but antibody E could also compete capsids off itself and antibody 14, likely by inducing capsid structural changes. In some cases, the initial TfR or antibody binding event affected subsequent TfR binding, suggesting that capsid structure changes occur after TfR or antibody binding and may impact infection. This shows that precise, host-specific TfR-capsid interactions, beyond simple attachment, are important for successful infection. Host receptor binding is a key step during viral infection and may control both infection and host range. In addition to binding, some viruses require specific interactions with host receptors in order to infect, and anti-capsid antibodies can potentially disrupt these interactions, leading to neutralization. Here, we examine the interactions between parvovirus capsids, the receptors from different hosts, and anti-capsid antibodies. We show that interactions between parvovirus capsids and host-specific TfRs vary in both affinity and in the numbers of receptors bound, with complex effects on infection. In addition, antibodies binding to two sites on the capsids had different effects on TfR-capsid binding. These experiments confirm that receptor and antibody binding to parvovirus capsids are complex processes, and the infection outcome is not determined simply by the affinity of attachment.
Topics: Animals; Antibodies, Viral; Capsid; Capsid Proteins; Cats; Cell Line; Dogs; Host Specificity; Humans; Jackals; Models, Molecular; Mutation; Parvovirus; Raccoons; Receptors, Transferrin
PubMed: 29695427
DOI: 10.1128/JVI.00460-18 -
Viruses Oct 2023The XVIII International Parvovirus Workshop took place in Rimini, Italy, from 14 to 17 June 2022 as an on-site event, continuing the series of meetings started in 1985...
The XVIII International Parvovirus Workshop took place in Rimini, Italy, from 14 to 17 June 2022 as an on-site event, continuing the series of meetings started in 1985 and continuously held every two years. The communications dealt with all aspects of research in the field, from evolution and structure to receptors, from replication to trafficking, from virus-host interactions to clinical and veterinarian virology, including translational issues related to viral vectors, gene therapy and oncolytic parvoviruses. The oral communications were complemented by a poster exhibition available for view and discussion during the whole meeting. The XVIII International Parvovirus Workshop was dedicated to the memory of our dearest colleague Mavis Agbandje-McKenna (1963-2021).
Topics: Humans; Parvovirus; Parvoviridae Infections; Genetic Vectors; Italy
PubMed: 37896906
DOI: 10.3390/v15102129 -
Molecular Therapy : the Journal of the... Dec 2021Parvoviruses and especially the adeno-associated virus (AAV) species provide an exciting and versatile platform for the rational design or molecular evolution of human... (Review)
Review
Parvoviruses and especially the adeno-associated virus (AAV) species provide an exciting and versatile platform for the rational design or molecular evolution of human gene-therapy vectors, documented by literature from over half a century, hundreds of clinical trials, and the recent commercialization of multiple AAV gene therapeutics. For the last three decades, the power of these vectors has been further potentiated through various types of hybrid vectors created by intra- or inter-genus juxtaposition of viral DNA and protein cis elements or by synergistic complementation of parvoviral features with those of heterologous, prokaryotic, or eukaryotic viruses. Here, we provide an overview of the history and promise of this rapidly expanding field of hybrid parvoviral gene-therapy vectors, starting with early generations of chimeric particles composed of a recombinant AAV genome encapsidated in shells of synthetic AAVs or of adeno-, herpes-, baculo-, or protoparvoviruses. We then dedicate our attention to two newer, highly promising types of hybrid vectors created via (1) pseudotyping of AAV genomes with bocaviral serotypes and capsid mutants or (2) packaging of AAV DNA into, or tethering of entire vector particles to, bacteriophages. Finally, we conclude with an outlook summarizing critical requirements and improvements toward clinical translation of these original concepts.
Topics: DNA, Viral; Dependovirus; Genetic Therapy; Genetic Vectors; Humans; Parvovirus
PubMed: 33831556
DOI: 10.1016/j.ymthe.2021.04.005 -
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 -
Nature Communications Jun 2023Parvoviruses (family Parvoviridae) are currently defined by a linear monopartite ssDNA genome, T = 1 icosahedral capsids, and distinct structural (VP) and...
Parvoviruses (family Parvoviridae) are currently defined by a linear monopartite ssDNA genome, T = 1 icosahedral capsids, and distinct structural (VP) and non-structural (NS) protein expression cassettes within their genome. We report the discovery of a parvovirus with a bipartite genome, Acheta domesticus segmented densovirus (AdSDV), isolated from house crickets (Acheta domesticus), in which it is pathogenic. We found that the AdSDV harbors its NS and VP cassettes on two separate genome segments. Its vp segment acquired a phospholipase A2-encoding gene, vpORF3, via inter-subfamily recombination, coding for a non-structural protein. We showed that the AdSDV evolved a highly complex transcription profile in response to its multipartite replication strategy compared to its monopartite ancestors. Our structural and molecular examinations revealed that the AdSDV packages one genome segment per particle. The cryo-EM structures of two empty- and one full-capsid population (3.3, 3.1 and 2.3 Å resolution) reveal a genome packaging mechanism, which involves an elongated C-terminal tail of the VP, "pinning" the ssDNA genome to the capsid interior at the twofold symmetry axis. This mechanism fundamentally differs from the capsid-DNA interactions previously seen in parvoviruses. This study provides new insights on the mechanism behind ssDNA genome segmentation and on the plasticity of parvovirus biology.
Topics: Animals; Densovirus; Gryllidae; Parvoviridae Infections; Morphogenesis; Capsid Proteins; DNA, Single-Stranded; Parvovirus
PubMed: 37316488
DOI: 10.1038/s41467-023-38875-x -
Viruses Jul 2021Since 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...
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.
Topics: Animals; Biopsy; Cohort Studies; DNA, Viral; Hepatitis, Viral, Animal; Horse Diseases; Horses; Liver; Longitudinal Studies; Parvoviridae Infections; Parvovirus; Persistent Infection; Phylogeny; Viremia
PubMed: 34452320
DOI: 10.3390/v13081454 -
Scientific Reports Jul 2020Ducks can shed and disseminate viruses and thus play a role in cross-species transmission. In the current study, we detected and characterised various avian parvoviruses...
Ducks can shed and disseminate viruses and thus play a role in cross-species transmission. In the current study, we detected and characterised various avian parvoviruses and picornaviruses from wild Pacific black ducks, Chestnut teals, Grey teals and Wood ducks sampled at multiple time points from a single location using metagenomics. We characterised 46 different avian parvoviruses belonging to three different genera Dependoparvovirus, Aveparvovirus and Chaphamaparvovirus, and 11 different avian picornaviruses tentatively belonging to four different genera Sicinivirus, Anativirus, Megrivirus and Aalivirus. Most of these viruses were genetically different from other currently known viruses from the NCBI dataset. The study showed that the abundance and number of avian picornaviruses and parvoviruses varied considerably throughout the year, with the high number of virus reads in some of the duck samples highly suggestive of an active infection at the time of sampling. The detection and characterisation of several parvoviruses and picornaviruses from the individual duck samples also suggests co-infection, which may lead to the emergence of novel viruses through possible recombination. Therefore, as new and emerging diseases evolve, it is relevant to explore and monitor potential animal reservoirs in their natural habitat.
Topics: Animals; Animals, Wild; Australia; Coinfection; Ducks; Ecosystem; Genome, Viral; Metagenomics; Parvoviridae Infections; Parvovirus; Picornaviridae; Picornaviridae Infections; Poultry Diseases
PubMed: 32733035
DOI: 10.1038/s41598-020-69557-z -
Viruses Jul 2022Porcine Parvovirus (PPV) is one of the most important infectious agents causing severe reproductive failure in pigs. In the last two decades a particular, a novel...
Porcine Parvovirus (PPV) is one of the most important infectious agents causing severe reproductive failure in pigs. In the last two decades a particular, a novel genotype emerged in Europe and PPV-27a was named as the prototype of this genetic cluster. It was suggested that members of the PPV-27a cluster may adversely influence effective vaccination against PPV. For a reliable updated 27a definition, we aligned 93 databank-deposited partial or full nucleotide and protein sequences of the VP2 of different PPV isolates. We confirmed that the 27a cluster could indeed be distinguished from other members of the species, however, some divergences were identified compared to earlier defined genetic markers. Based on genetic differences, we developed a dual allele-specific polymerase chain reaction for the easy and quick discrimination of members of the 27a cluster from other PPV strains. The detection limit of dual PCR was found <1.66 × 104 copies/reaction. To sensitize and make it more user friendly, the method was further developed for qPCR application with fluorescent probes. Regarding the detection limit of the two PCRs (<1.66 × 104 copies/reaction of the dual PCR versus <2.40 × 102 copy/reaction of the dual qPCR), approximately two log improvement was achieved in the sensitivity of the method.
Topics: Alleles; Amino Acid Sequence; Animals; Parvoviridae Infections; Parvovirus, Porcine; Real-Time Polymerase Chain Reaction; Swine; Swine Diseases
PubMed: 35891481
DOI: 10.3390/v14071500 -
Virology Journal Dec 2014Parvoviruses are classified into two subfamilies based on their host range: the Parvovirinae, which infect vertebrates, and the Densovirinae, which mainly infect insects...
BACKGROUND
Parvoviruses are classified into two subfamilies based on their host range: the Parvovirinae, which infect vertebrates, and the Densovirinae, which mainly infect insects and other arthropods. In recent years, a number of novel parvoviruses belonging to the subfamily Parvovirinae have been identified from various animal species and humans, including human parvovirus 4 (PARV4), porcine hokovirus, ovine partetravirus, porcine parvovirus 4 (PPV4), and porcine parvovirus 5 (PPV5).
METHODS
Using sequence-independent single primer amplification (SISPA), a novel parvovirus within the subfamily Parvovirinae that was distinct from any known parvoviruses was identified and five full-length genome sequences were determined and analyzed.
RESULTS
A novel porcine parvovirus, provisionally named PPV6, was initially identified from aborted pig fetuses in China. Retrospective studies revealed the prevalence of PPV6 in aborted pig fetuses and piglets(50% and 75%, respectively) was apparently higher than that in finishing pigs and sows (15.6% and 3.8% respectively). Furthermore, the prevalence of PPV6 in finishing pig was similar in affected and unaffected farms (i.e. 16.7% vs. 13.6%-21.7%). This finding indicates that animal age, perhaps due to increased innate immune resistance, strongly influences the level of PPV6 viremia. Complete genome sequencing and multiple alignments have shown that the nearly full-length genome sequences were approximately 6,100 nucleotides in length and shared 20.5%-42.6% DNA sequence identity with other members of the Parvovirinae subfamily. Phylogenetic analysis showed that PPV6 was significantly distinct from other known parvoviruses and was most closely related to PPV4.
CONCLUSION
Our findings and review of published parvovirus sequences suggested that a novel porcine parvovirus is currently circulating in China and might be classified into the novel genus Copiparvovirus within the subfamily Parvovirinae. However, the clinical manifestations of PPV6 are still unknown in that the prevalence of PPV6 was similar between healthy pigs and sick pigs in a retrospective epidemiological study. The identification of PPV6 within the subfamily Parvovirinae provides further insight into the viral and genetic diversity of parvoviruses.
Topics: Animals; China; Cluster Analysis; DNA, Viral; Genome, Viral; Molecular Sequence Data; Parvoviridae Infections; Parvovirus, Porcine; Phylogeny; Sequence Analysis, DNA; Sequence Homology; Swine; Swine Diseases
PubMed: 25442288
DOI: 10.1186/s12985-014-0203-2