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Viruses Jul 2021Parvoviruses are small single-stranded (ss) DNA viruses, which replicate in the nucleoplasm and affect both the structure and function of the nucleus. The nuclear stage... (Review)
Review
Parvoviruses are small single-stranded (ss) DNA viruses, which replicate in the nucleoplasm and affect both the structure and function of the nucleus. The nuclear stage of the parvovirus life cycle starts at the nuclear entry of incoming capsids and culminates in the successful passage of progeny capsids out of the nucleus. In this review, we will present past, current, and future microscopy and biochemical techniques and demonstrate their potential in revealing the dynamics and molecular interactions in the intranuclear processes of parvovirus infection. In particular, a number of advanced techniques will be presented for the detection of infection-induced changes, such as DNA modification and damage, as well as protein-chromatin interactions.
Topics: Animals; Capsid Proteins; Cell Nucleus; Host Microbial Interactions; Humans; Mice; Parvoviridae Infections; Parvovirus; Virus Replication
PubMed: 34372512
DOI: 10.3390/v13071306 -
Viruses Oct 2021We introduce Viral Phrenology, a new scheme for understanding the genomic composition of spherical viruses based on the locations of their structural protrusions. We...
We introduce Viral Phrenology, a new scheme for understanding the genomic composition of spherical viruses based on the locations of their structural protrusions. We used icosahedral point arrays to classify 135 distinct viral capsids collected from over 600 capsids available in the VIPERdb. Using gauge points of point arrays, we found 149 unique structural protrusions. We then show how to use the locations of these protrusions to determine the genetic composition of the virus. We then show that ssDNA, dsDNA, dsRNA and ssRNA viruses use different arrangements for distributing their protrusions. We also found that Triangulation number is also partially dependent on the structural protrusions. This analysis begins to tie together Baltimore Classification and Triangulation number using point arrays.
Topics: Capsid; Cryoelectron Microscopy; Crystallography, X-Ray; DNA, Single-Stranded; Genome, Viral; Models, Molecular; Nanomedicine; Norovirus; Parvoviridae; Phrenology; RNA, Double-Stranded; Virion; Viruses
PubMed: 34834999
DOI: 10.3390/v13112191 -
Molecular Microbiology Oct 2022Parvoviruses are small non-enveloped single-stranded DNA viruses, which depend on host cell nuclear transcriptional and replication machinery. After endosomal exposure... (Review)
Review
Parvoviruses are small non-enveloped single-stranded DNA viruses, which depend on host cell nuclear transcriptional and replication machinery. After endosomal exposure of nuclear localization sequence and a phospholipase A domain on the capsid surface, and escape into the cytosol, parvovirus capsids enter the nucleus. Due to the small capsid diameter of 18-26 nm, intact capsids can potentially pass into the nucleus through nuclear pore complexes (NPCs). This might be facilitated by active nuclear import, but capsids may also follow an alternative entry pathway that includes activation of mitotic factors and local transient disruption of the nuclear envelope. The nuclear entry is followed by currently undefined events of viral genome uncoating. After genome release, viral replication compartments are initiated and infection proceeds. Parvoviral genomes replicate during cellular S phase followed by nuclear capsid assembly during virus-induced S/G2 cell cycle arrest. Nuclear egress of capsids occurs upon nuclear envelope degradation during apoptosis and cell lysis. An alternative pathway for nuclear export has been described using active transport through the NPC mediated by the chromosome region maintenance 1 protein, CRM1, which is enhanced by phosphorylation of the N-terminal domain of VP2. However, other alternative but not yet uncharacterized nuclear export pathways cannot be excluded.
Topics: DNA, Single-Stranded; Virus Replication; Parvovirus; Cell Nucleus; Active Transport, Cell Nucleus; Nuclear Pore; Nuclear Envelope; Capsid Proteins; Phospholipases
PubMed: 35974704
DOI: 10.1111/mmi.14974 -
Hematology/oncology and Stem Cell... Dec 2019
Topics: Adult; Humans; Male; Parvoviridae Infections; Parvovirus B19, Human; Thrombocytopenia
PubMed: 29908911
DOI: 10.1016/j.hemonc.2018.05.003 -
Journal of Virology Jul 2023Adeno-associated virus (AAV) is a nonenveloped single-stranded DNA (ssDNA) icosahedral T=1 virus being developed as a vector for clinical gene delivery systems....
Adeno-associated virus (AAV) is a nonenveloped single-stranded DNA (ssDNA) icosahedral T=1 virus being developed as a vector for clinical gene delivery systems. Currently, there are approximately 160 AAV clinical trials, with AAV2 being the most widely studied serotype. To further understand the AAV gene delivery system, this study investigates the role of viral protein (VP) symmetry interactions on capsid assembly, genome packaging, stability, and infectivity. A total of 25 (seven 2-fold, nine 3-fold, and nine 5-fold symmetry interface) AAV2 VP variants were studied. Six 2-fold and two 5-fold variants did not assemble capsids based on native immunoblots and anti-AAV2 enzyme-linked immunosorbent assays (ELISAs). Seven of the 3-fold and seven of the 5-fold variants that assembled capsids were less stable, while the only 2-fold variant that assembled had ~2°C higher thermal stability () than recombinant wild-type AAV2 (wtAAV2). Three of the 3-fold variants (AAV2-R432A, AAV2-L510A, and N511R) had an approximately 3-log defect in genome packaging. Consistent with previous reports of the 5-fold axes, the region of the capsid is important for VP1u externalization and genome ejection, and one 5-fold variant (R404A) had a significant defect in viral infectivity. The structures of wtAAV2 packaged with a transgene (AAV2-full) and without a transgene (AAV2-empty) and one 5-fold variant (AAV2-R404A) were determined by cryo-electron microscopy and three dimensional (3D)-image reconstruction to 2.8, 2.9, and 3.6 Å resolution, respectively. These structures revealed the role of stabilizing interactions on the assembly, stability, packaging, and infectivity of the virus capsid. This study provides insight into the structural characterization and functional implications of the rational design of AAV vectors. Adeno-associated viruses (AAVs) have been shown to be useful vectors for gene therapy applications. Consequently, AAV has been approved as a biologic for the treatment of several monogenic disorders, and many additional clinical trials are ongoing. These successes have generated significant interest in all aspects of the basic biology of AAV. However, to date, there are limited data available on the importance of the capsid viral protein (VP) symmetry-related interactions required to assemble and maintain the stability of the AAV capsids and the infectivity of the AAV capsids. Characterizing the residue type and interactions at these symmetry-driven assembly interfaces of AAV2 has provided the foundation for understanding their role in AAV vectors (serotypes and engineered chimeras) and has determined the residues or regions of the capsid that can or cannot tolerate alterations.
Topics: Capsid; Dependovirus; Serogroup; Cryoelectron Microscopy; Capsid Proteins; Parvovirinae; Viral Proteins; Genetic Vectors; Virus Assembly
PubMed: 37310260
DOI: 10.1128/jvi.01772-22 -
Archives of Virology May 2022In this study, genetic counterparts of the human-stool-associated tusavirus (subfamily Parvovirinae, family Parvoviridae) with >97% and 95-100% amino acid sequence...
In this study, genetic counterparts of the human-stool-associated tusavirus (subfamily Parvovirinae, family Parvoviridae) with >97% and 95-100% amino acid sequence identity in the parvoviral NS1 and VP1 protein were identified in faecal specimens from domestic goats (Capra hircus) and sheep (Ovis aries) in Hungary. Eleven (17.8%) of the 62 faecal specimens from goats and 12 (25.5%) of the 47 from sheep both from less than 12 months old animals were positive for tusavirus DNA by PCR, while none of the specimens collected from cattle and swine were positive. Thus, it cannot be ruled out that tusavirus infection in humans is of zoonotic origin.
Topics: Animals; Cattle; Feces; Goats; Humans; Parvoviridae; Parvovirinae; Parvovirus; Sheep; Swine
PubMed: 35355143
DOI: 10.1007/s00705-022-05424-8 -
Viruses Jun 2023Cats harbor many important viral pathogens, and the knowledge of their diversity has been greatly expanded thanks to increasingly popular molecular sequencing... (Review)
Review
Cats harbor many important viral pathogens, and the knowledge of their diversity has been greatly expanded thanks to increasingly popular molecular sequencing techniques. While the diversity is mostly described in numerous regionally defined studies, there lacks a global overview of the diversity for the majority of cat viruses, and therefore our understanding of the evolution and epidemiology of these viruses was generally inadequate. In this study, we analyzed 12,377 genetic sequences from 25 cat virus species and conducted comprehensive phylodynamic analyses. It revealed, for the first time, the global diversity for all cat viruses known to date, taking into account highly virulent strains and vaccine strains. From there, we further characterized and compared the geographic expansion patterns, temporal dynamics and recombination frequencies of these viruses. While respiratory pathogens such as feline calicivirus showed some degree of geographical panmixes, the other viral species are more geographically defined. Furthermore, recombination rates were much higher in feline parvovirus, feline coronavirus, feline calicivirus and feline foamy virus than the other feline virus species. Collectively, our findings deepen the understanding of the evolutionary and epidemiological features of cat viruses, which in turn provide important insight into the prevention and control of cat pathogens.
Topics: Animals; Cats; Calicivirus, Feline; Cat Diseases; Feline Panleukopenia Virus; Genetic Variation
PubMed: 37376637
DOI: 10.3390/v15061338 -
Viruses Jun 2021Parvovirus infections in cats have been well known for around 100 years. Recently, the use of molecular assays and metagenomic approaches for virus discovery and... (Review)
Review
Parvovirus infections in cats have been well known for around 100 years. Recently, the use of molecular assays and metagenomic approaches for virus discovery and characterization has led to the detection of novel parvovirus lineages and/or species infecting the feline host. However, the involvement of emerging parvoviruses in the onset of gastroenteritis or other feline diseases is still uncertain.
Topics: Animals; Animals, Domestic; Cat Diseases; Cats; Metagenomics; Parvoviridae Infections; Parvovirus; Phylogeny
PubMed: 34200079
DOI: 10.3390/v13061077 -
Viral Immunology May 2020When an individual is exposed to a viral pathogen for the first time, the adaptive immune system is naive and cannot prevent virus replication. The consequence may be... (Review)
Review
When an individual is exposed to a viral pathogen for the first time, the adaptive immune system is naive and cannot prevent virus replication. The consequence may be severe disease. At the same time, the host may rapidly generate a pathogen-specific immune response that will prevent disease if the virus is encountered again. Parvovirus B19 provides one such example. Children with sickle cell disease can experience life-threatening transient aplastic crisis when first exposed to parvovirus B19, but an effective immune response confers lifelong protection. We briefly examine the induction and benefits of virus-induced immunity. We focus on three human viruses for which there are no licensed vaccines (respiratory syncytial virus, human immunodeficiency virus type 1, and parvovirus B19) and consider how virus-induced immunity may inform successful vaccine design.
Topics: AIDS Vaccines; HIV Infections; HIV-1; Humans; Immunity; Parvoviridae Infections; Parvovirus B19, Human; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Viruses
PubMed: 32366204
DOI: 10.1089/vim.2019.0138 -
Science Translational Medicine Jul 2023Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a...
Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high-throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children's of Alabama and compared their antibody responses with 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and adeno-associated virus 2 (AAV-2) peptide responses that were conserved in seven of nine cases but rarely observed in pediatric and adult controls. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.
Topics: Adult; Humans; Child; Dependovirus; Hepatitis; Liver Diseases
PubMed: 37494473
DOI: 10.1126/scitranslmed.adh9917