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Frontiers in Immunology 2024Parvoviruses are a group of non-enveloped DNA viruses that have a broad spectrum of natural infections, making them important in public health. NS1 is the largest and... (Review)
Review
Parvoviruses are a group of non-enveloped DNA viruses that have a broad spectrum of natural infections, making them important in public health. NS1 is the largest and most complex non-structural protein in the parvovirus genome, which is indispensable in the life cycle of parvovirus and is closely related to viral replication, induction of host cell apoptosis, cycle arrest, DNA damage response (DDR), and other processes. Parvovirus activates and utilizes the DDR pathway to promote viral replication through NS1, thereby increasing pathogenicity to the host cells. Here, we review the latest progress of parvovirus in regulating host cell DDR during the parvovirus lifecycle and discuss the potential of cellular consequences of regulating the DDR pathway, targeting to provide the theoretical basis for further elucidation of the pathogenesis of parvovirus and development of new antiviral drugs.
Topics: Humans; Parvovirus; Parvoviridae Infections; Virus Replication; Parvovirus B19, Human; DNA Repair
PubMed: 38464523
DOI: 10.3389/fimmu.2024.1324531 -
PLoS Pathogens May 2023The oncolytic autonomous parvovirus Minute Virus of Mice (MVM) establishes infection in the nuclear environment by usurping host DNA damage signaling proteins in the...
The oncolytic autonomous parvovirus Minute Virus of Mice (MVM) establishes infection in the nuclear environment by usurping host DNA damage signaling proteins in the vicinity of cellular DNA break sites. MVM replication induces a global cellular DNA Damage Response (DDR) that is dependent on signaling by the ATM kinase and inactivates the cellular ATR-kinase pathway. However, the mechanism of how MVM generates cellular DNA breaks remains unknown. Using single molecule DNA Fiber Analysis, we have discovered that MVM infection leads to a shortening of host replication forks as infection progresses, as well as induction of replication stress prior to the initiation of virus replication. Ectopically expressed viral non-structural proteins NS1 and NS2 are sufficient to cause host-cell replication stress, as is the presence of UV-inactivated non-replicative MVM genomes. The host single-stranded DNA binding protein Replication Protein A (RPA) associates with the UV-inactivated MVM genomes, suggesting MVM genomes might serve as a sink for cellular stores of RPA. Overexpressing RPA in host cells prior to UV-MVM infection rescues DNA fiber lengths and increases MVM replication, confirming that MVM genomes deplete RPA stores to cause replication stress. Together, these results indicate that parvovirus genomes induce replication stress through RPA exhaustion, rendering the host genome vulnerable to additional DNA breaks.
Topics: Animals; Mice; Minute Virus of Mice; Replication Protein A; Parvovirus; Virus Replication; Parvoviridae Infections; DNA Replication
PubMed: 37253065
DOI: 10.1371/journal.ppat.1011203 -
Current Topics in Microbiology and... 2006The Parvoviridae, a family of viruses with single-stranded DNA genomes widely spread from invertebrates to mammal and human hosts, display a remarkable evolutionary... (Review)
Review
The Parvoviridae, a family of viruses with single-stranded DNA genomes widely spread from invertebrates to mammal and human hosts, display a remarkable evolutionary capacity uncommon in DNA genomes. Parvovirus populations show high genetic heterogeneity and large population sizes resembling the quasispecies found in RNA viruses. These viruses multiply in proliferating cells, causing acute, persistent or latent infections relying in the immunocompetence and developmental stage of the hosts. Some parvovirus populations in natural settings, such as carnivore autonomous parvoviruses or primate adeno associated virus, show a high degree of genetic heterogeneity. However, other parvoviruses such as the pathogenic B19 human erythrovirus or the porcine parvovirus, show little genetic variation, indicating different virus-host relationships. The Parvoviridae evolutionary potential in mammal infections has been modeled in the experimental system formed by the immunodeficient scid mouse infected by the minute virus of mice (MVM) under distinct immune and adaptive pressures. The sequence of viral genomes (close to 10(5) nucleotides) in emerging MVM pathogenic populations present in the organs of 26 mice showed consensus sequences not representing the complex distribution of viral clones and a high genetic heterogeneity (average mutation frequency 8.3 x 10(-4) substitutions/nt accumulated over 2-3 months). Specific amino acid changes, selected at a rate up to 1% in the capsid and in the NS2 nonstructural protein, endowed these viruses with new tropism and increased fitness. Further molecular analysis supported the notion that, in addition to immune pressures, the affinity of molecular interactions with cellular targets, as the Crml nuclear export receptor or the primary capsid receptor, as well as the adaptation to tissues enriched in proliferating cells, are major selective factors in the rapid parvovirus evolutionary dynamics.
Topics: Animals; Capsid; Evolution, Molecular; Genetic Variation; Genome, Viral; Humans; Parvoviridae Infections; Parvovirus; RNA Viruses; Virus Replication
PubMed: 16568906
DOI: 10.1007/3-540-26397-7_13 -
Journal of Virology Jul 2004
Review
Topics: Animals; Cell Line; Dependovirus; Dogs; Humans; Mice; Parvoviridae Infections; Parvovirus
PubMed: 15194745
DOI: 10.1128/JVI.78.13.6709-6714.2004 -
Reviews in Medical Virology 2006
Topics: History, 20th Century; History, 21st Century; Humans; Parvoviridae Infections; Parvovirus
PubMed: 16933367
DOI: 10.1002/rmv.511 -
Human Gene Therapy Mar 2019
Topics: Gene Transfer Techniques; Genetic Engineering; Genetic Therapy; Genetic Vectors; Humans; Parvovirus
PubMed: 30807259
DOI: 10.1089/hum.2019.29084.mam -
Journal of the American Veterinary... Feb 2022To compare the serum cobalamin concentrations in canine parvovirus (CPV)-infected dogs with those of healthy control dogs.
OBJECTIVE
To compare the serum cobalamin concentrations in canine parvovirus (CPV)-infected dogs with those of healthy control dogs.
ANIMALS
45 dogs with CPV enteritis and 17 healthy age-matched control dogs.
PROCEDURES
Infection was confirmed by visualization of CPV-2 through fecal electron microscopy. All dogs received supportive care. Serum samples taken at admission were used to determine cobalamin, C-reactive protein, and albumin concentrations.
RESULTS
Serum cobalamin concentrations were significantly lower in the CPV-infected group (median [interquartile range], 173 pmol/L [< 111 to 722 pmol/L]) than in healthy control dogs (379 pmol/L [193 to > 738 pmol/L). There was no association between cobalamin concentration and C-reactive protein or albumin concentration.
CLINICAL RELEVANCE
While hypocobalaminemia was common in CPV-infected dogs, the clinical relevance of this finding remains to be determined. Studies assessing markers of cellular cobalamin deficiency in dogs with CPV infection appear warranted.
Topics: Animals; C-Reactive Protein; Dog Diseases; Dogs; Enteritis; Parvoviridae Infections; Parvovirus; Parvovirus, Canine; Vitamin B 12
PubMed: 35113794
DOI: 10.2460/javma.21.05.0240 -
Acta Veterinaria Hungarica 1999Parvoviruses have small genomes and, consequently, are highly dependent on their host for various functions in their reproduction. Since these viruses generally use... (Review)
Review
Parvoviruses have small genomes and, consequently, are highly dependent on their host for various functions in their reproduction. Since these viruses generally use ubiquitous receptors, restrictions are usually intracellularly regulated. A lack of mitosis, and hence absence of enzymes required for DNA replication, is a powerful block of virus infection. Allotropic determinants have been identified for several parvoviruses: porcine parvovirus, canine parvovirus (CPV), feline parvovirus (feline panleukopenia virus), minute virus of mice, Aleutian disease virus, and GmDNV (an insect parvovirus). Invariably, these identifications involved the use of infectious clones of these viruses and the exchange of restriction fragments to create chimeric viruses, of which the resulting phenotype was then established by transfection in appropriate cell lines. The tropism of these viruses was found to be governed by minimal changes in the sequence of the capsid proteins and, often, only 2 or 3 critical amino acids are responsible for a given tropism. These amino acids are usually located on the outside of the capsid near or on the spike of the threefold axis for the vertebrate parvoviruses and on loops 2 or 3 for the insect parvoviruses. This tropism is not mediated via specific cellular receptors but by interactions with intracellular factors. The nature of these factors is unknown but most data point to a stage beyond the conversion of the single-stranded DNA genome by host cell DNA polymerase into monomeric duplex intermediates of the replicative form. The sudden and devastating emergence of mink enteritis virus (MEV) and CPV in the last 50 years, and the possibility of more future outbreaks, demonstrates the importance of understanding parvovirus tropism.
Topics: Animals; Cats; Computer Simulation; Dogs; Mice; Parvovirus; Structure-Activity Relationship; Tropism; Virus Replication
PubMed: 10497831
DOI: 10.1556/AVet.47.1999.3.11 -
Australian Veterinary Journal 2005
Topics: Animals; Dog Diseases; Dogs; Parvoviridae Infections; Parvovirus; Queensland; Vaccines, Inactivated; Viral Vaccines
PubMed: 15971810
DOI: No ID Found -
Comparative Medicine Oct 2003
Review
Topics: Animals; Mice; Minute Virus of Mice; Parvoviridae Infections; Rodent Diseases; Serologic Tests
PubMed: 14655987
DOI: No ID Found