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Special Issue "Protoparvoviruses: Friends or Foes?"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 January 2018)

Special Issue Editors

Guest Editor
Dr. Christiane Dinsart

DKFZ, Abt F010, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany
Website | E-Mail
Guest Editor
Dr. Jürg Nüesch

DKFZ, Abt F010, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany
Website | E-Mail

Special Issue Information

Dear Colleagues,

Over the last few decades, accumulating evidence has demonstrated that some members of the Parvoviridae family, in particular some rodent Protoparvoviruses have natural anticancer activities, while being nonpathogenic to humans. Based on in vitro and pre-clinical studies a first phase I/IIa clinical trial of rat H-1PV was conducted in patients with glioblastoma multiforme. Novel parvovirus-based anticancer strategies with enhanced specificity and efficacy are currently under investigation.

However, a number of Parvoviruses cause diseases in humans and animals. Recently, deep sequencing and metagenomic techniques have allowed the discovery of several novel parvoviruses, suspected of being pathogenic; in particular bufaviruses, which were assigned to the genus Protoparvovirus.

While Protoparvoviruses have a low genetic complexity, many steps of the virus cycle are still not completely understood. This Special Issue of Viruses will explore the impact of Protoparvovirus evolution on the outcome of the interactions of these agents with host cells and organisms. Topics may include studies on various steps of the viral cycle, virus adaptation, immune responses to infection and mechanisms of virus immune evasion, clinical presentation of virus infection, and strategies for vaccine development.

Dr. Christiane Dinsart
Dr. Jürg Nüesch
Guest editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Protoparvoviruses
  • Parvovirus-host cell interaction
  • Parvovirus adaptation/evolution
  • New parvoviral pathogens
  • Parvoviral therapeutics and vaccines

Published Papers (13 papers)

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Research

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Open AccessArticle Preclinical Testing of an Oncolytic Parvovirus in Ewing Sarcoma: Protoparvovirus H-1 Induces Apoptosis and Lytic Infection In Vitro but Fails to Improve Survival In Vivo
Viruses 2018, 10(6), 302; https://doi.org/10.3390/v10060302
Received: 2 May 2018 / Revised: 27 May 2018 / Accepted: 29 May 2018 / Published: 3 June 2018
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Abstract
About 70% of all Ewing sarcoma (EWS) patients are diagnosed under the age of 20 years. Over the last decades little progress has been made towards finding effective treatment approaches for primarily metastasized or refractory Ewing sarcoma in young patients. Here, in the
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About 70% of all Ewing sarcoma (EWS) patients are diagnosed under the age of 20 years. Over the last decades little progress has been made towards finding effective treatment approaches for primarily metastasized or refractory Ewing sarcoma in young patients. Here, in the context of the search for novel therapeutic options, the potential of oncolytic protoparvovirus H-1 (H-1PV) to treat Ewing sarcoma was evaluated, its safety having been proven previously tested in adult cancer patients and its oncolytic efficacy demonstrated on osteosarcoma cell cultures. The effects of viral infection were tested in vitro on four human Ewing sarcoma cell lines. Notably evaluated were effects of the virus on the cell cycle and its replication efficiency. Within 24 h after infection, the synthesis of viral proteins was induced. Efficient H-1PV replication was confirmed in all four Ewing sarcoma cell lines. The cytotoxicity of the virus was determined on the basis of cytopathic effects, cell viability, and cell lysis. These in vitro experiments revealed efficient killing of Ewing sarcoma cells by H-1PV at a multiplicity of infection between 0.1 and 5 plaque forming units (PFU)/cell. In two of the four tested cell lines, significant induction of apoptosis by H-1PV was observed. H-1PV thus meets all the in vitro criteria for a virus to be oncolytic towards Ewing sarcoma. In the first xenograft experiments, however, although an antiproliferative effect of intratumoral H-1PV injection was observed, no significant improvement of animal survival was noted. Future projects aiming to validate parvovirotherapy for the treatment of pediatric Ewing sarcoma should focus on combinatorial treatments and will require the use of patient-derived xenografts and immunocompetent syngeneic animal models. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessArticle Mutations in the Non-Structural Protein-Coding Sequence of Protoparvovirus H-1PV Enhance the Fitness of the Virus and Show Key Benefits Regarding the Transduction Efficiency of Derived Vectors
Viruses 2018, 10(4), 150; https://doi.org/10.3390/v10040150
Received: 26 January 2018 / Revised: 23 March 2018 / Accepted: 26 March 2018 / Published: 27 March 2018
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Abstract
Single nucleotide changes were introduced into the non-structural (NS) coding sequence of the H-1 parvovirus (PV) infectious molecular clone and the corresponding virus stocks produced, thereby generating H1-PM-I, H1-PM-II, H1-PM-III, and H1-DM. The effects of the mutations on viral fitness were analyzed. Because
[...] Read more.
Single nucleotide changes were introduced into the non-structural (NS) coding sequence of the H-1 parvovirus (PV) infectious molecular clone and the corresponding virus stocks produced, thereby generating H1-PM-I, H1-PM-II, H1-PM-III, and H1-DM. The effects of the mutations on viral fitness were analyzed. Because of the overlapping sequences of NS1 and NS2, the mutations affected either NS2 (H1-PM-II, -III) or both NS1 and NS2 proteins (H1-PM-I, H1-DM). Our results show key benefits of PM-I, PM-II, and DM mutations with regard to the fitness of the virus stocks produced. Indeed, these mutants displayed a higher production of infectious virus in different cell cultures and better spreading capacity than the wild-type virus. This correlated with a decreased particle-to-infectivity (P/I) ratio and stimulation of an early step(s) of the viral cycle prior to viral DNA replication, namely, cell binding and internalization. These mutations also enhance the transduction efficiency of H-1PV-based vectors. In contrast, the PM-III mutation, which affects NS2 at a position downstream of the sequence deleted in Del H-1PV, impaired virus replication and spreading. We hypothesize that the NS2 protein—modified in H1-PM-I, H1-PM-II, and H1-DM—may result in the stimulation of some maturation step(s) of the capsid and facilitate virus entry into subsequently infected cells. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessArticle Optimizing the Targeting of Mouse Parvovirus 1 to Murine Melanoma Selects for Recombinant Genomes and Novel Mutations in the Viral Capsid Gene
Viruses 2018, 10(2), 54; https://doi.org/10.3390/v10020054
Received: 30 December 2017 / Revised: 23 January 2018 / Accepted: 27 January 2018 / Published: 30 January 2018
Cited by 1 | PDF Full-text (9607 KB) | HTML Full-text | XML Full-text
Abstract
Combining virus-enhanced immunogenicity with direct delivery of immunomodulatory molecules would represent a novel treatment modality for melanoma, and would require development of new viral vectors capable of targeting melanoma cells preferentially. Here we explore the use of rodent protoparvoviruses targeting cells of the
[...] Read more.
Combining virus-enhanced immunogenicity with direct delivery of immunomodulatory molecules would represent a novel treatment modality for melanoma, and would require development of new viral vectors capable of targeting melanoma cells preferentially. Here we explore the use of rodent protoparvoviruses targeting cells of the murine melanoma model B16F10. An uncloned stock of mouse parvovirus 1 (MPV1) showed some efficacy, which was substantially enhanced following serial passage in the target cell. Molecular cloning of the genes of both starter and selected virus pools revealed considerable sequence diversity. Chimera analysis mapped the majority of the improved infectivity to the product of the major coat protein gene, VP2, in which linked blocks of amino acid changes and one or other of two apparently spontaneous mutations were selected. Intragenic chimeras showed that these represented separable components, both contributing to enhanced infection. Comparison of biochemical parameters of infection by clonal viruses indicated that the enhancement due to changes in VP2 operates after the virus has bound to the cell surface and penetrated into the cell. Construction of an in silico homology model for MPV1 allowed placement of these changes within the capsid shell, and revealed aspects of the capsid involved in infection initiation that had not been previously recognized. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessCommunication Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity
Viruses 2017, 9(12), 382; https://doi.org/10.3390/v9120382
Received: 17 November 2017 / Revised: 8 December 2017 / Accepted: 11 December 2017 / Published: 15 December 2017
Cited by 4 | PDF Full-text (5480 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and
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Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood–brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessArticle Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
Viruses 2017, 9(11), 321; https://doi.org/10.3390/v9110321
Received: 16 October 2017 / Revised: 27 October 2017 / Accepted: 27 October 2017 / Published: 30 October 2017
Cited by 3 | PDF Full-text (13186 KB) | HTML Full-text | XML Full-text
Abstract
LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM,
[...] Read more.
LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3.17 Å resolution, and compared to the H-1PV and MVM structures. The LuIII VP2 structure, ordered from residue 37 to 587 (C-terminal), had the conserved VP topology and capsid morphology previously reported for other protoparvoviruses. This includes a core β-barrel and α-helix A, a depression at the icosahedral 2-fold and surrounding the 5-fold axes, and a single protrusion at the 3-fold axes. Comparative analysis identified surface loop differences among LuIII, H-1PV, and MVM at or close to the capsid 2- and 5-fold symmetry axes, and the shoulder of the 3-fold protrusions. The 2-fold differences cluster near the previously identified MVM sialic acid receptor binding pocket, and revealed potential determinants of protoparvovirus tumor tropism. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessArticle Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro
Viruses 2017, 9(10), 301; https://doi.org/10.3390/v9100301
Received: 1 September 2017 / Revised: 22 September 2017 / Accepted: 26 September 2017 / Published: 17 October 2017
Cited by 2 | PDF Full-text (3408 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A
[...] Read more.
Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal cells. H-1PV was found to enter osteosarcoma cells and to induce viral DNA replication, transcription of viral genes, and translation to viral proteins. After H-1PV infection, release of infectious viral particles from osteosarcoma cells into the supernatant indicated successful viral assembly and egress. Crystal violet staining revealed progressive cytomorphological changes in all osteosarcoma cell lines. Infection of osteosarcoma cell lines with the standard H-1PV caused an arrest of the cell cycle in the G2 phase, and these lines had a limited capacity for standard H-1PV virus replication. The cytotoxicity of wild-type H-1PV virus towards osteosarcoma cells was compared in vitro with that of two variants, Del H-1PV and DM H-1PV, previously described as fitness variants displaying higher infectivity and spreading in human transformed cell lines of different origins. Surprisingly, wild-type H-1PV displayed the strongest cytostatic and cytotoxic effects in this analysis and thus seems the most promising for the next preclinical validation steps in vivo. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessArticle Perspectives on the Evolution of Porcine Parvovirus
Viruses 2017, 9(8), 196; https://doi.org/10.3390/v9080196
Received: 13 June 2017 / Revised: 19 July 2017 / Accepted: 24 July 2017 / Published: 26 July 2017
Cited by 1 | PDF Full-text (6853 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Porcine parvovirus (PPV) is one of the main causes of porcine reproductive failure. It is important for swine industries to understand the recent trends in PPV evolution. Previous data show that PPV has two genetic lineages originating in Germany. In this study, two
[...] Read more.
Porcine parvovirus (PPV) is one of the main causes of porcine reproductive failure. It is important for swine industries to understand the recent trends in PPV evolution. Previous data show that PPV has two genetic lineages originating in Germany. In this study, two more genetic lineages were defined, one of which was distinctly Asian. Additionally, amino acid substitutions in European strains and Asian strains showed distinct differences in several regions of the VP2 gene. The VP1 gene of the recent PPV isolate (T142_South Korea) was identical to that of Kresse strain isolated in the USA in 1985, indicating that modern PPV strains now resemble the original strains (Kresse and NADL-2). In this study, we compared strains isolated in the 20th century to recent isolates and confirmed the trend that modern strains are becoming more similar to previous strains. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessArticle Impact of Parvovirus B19 Viremia in Liver Transplanted Children on Anemia: A Retrospective Study
Viruses 2017, 9(6), 149; https://doi.org/10.3390/v9060149
Received: 5 April 2017 / Revised: 30 May 2017 / Accepted: 6 June 2017 / Published: 13 June 2017
Cited by 2 | PDF Full-text (689 KB) | HTML Full-text | XML Full-text
Abstract
Acute parvovirus B19 (B19V) infection in immunocompromised patients may lead to severe anemia. However, in adult transplant recipients, B19V reactivations without anemia and low-level viremia are common. The impact of B19V in pediatric transplant patients, with high risk of primary infection, is investigated
[...] Read more.
Acute parvovirus B19 (B19V) infection in immunocompromised patients may lead to severe anemia. However, in adult transplant recipients, B19V reactivations without anemia and low-level viremia are common. The impact of B19V in pediatric transplant patients, with high risk of primary infection, is investigated here. In a six-month period, 159 blood samples of 54 pediatric liver transplant recipients were tested for B19V DNA by quantitative real-time PCR. Viremia was correlated with anemia and immunosuppression and compared with rates in adult transplant recipients. B19V DNA was detected in 5/54 patients. Primary B19V infections were observed in four patients prior to and in one patient after transplantation. Rates of viremia were significantly higher in pediatric recipients than in adults. Prolonged virus shedding after primary infection prior to transplantation accounts for most viremic cases. Anemia was significantly more frequent in samples from viremic patients, but remained mild. In 15% of anemic samples, B19V DNA was detected. Therefore, in anemic pediatric transplant recipients, diagnostics for B19V seem reasonable. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Review

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Open AccessReview Biology of Porcine Parvovirus (Ungulate parvovirus 1)
Viruses 2017, 9(12), 393; https://doi.org/10.3390/v9120393
Received: 1 December 2017 / Revised: 17 December 2017 / Accepted: 18 December 2017 / Published: 20 December 2017
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Abstract
Porcine parvovirus (PPV) is among the most important infectious agents causing infertility in pigs. Until recently, it was thought that the virus had low genetic variance, and that prevention of its harmful effect on pig fertility could be well-controlled by vaccination. However, at
[...] Read more.
Porcine parvovirus (PPV) is among the most important infectious agents causing infertility in pigs. Until recently, it was thought that the virus had low genetic variance, and that prevention of its harmful effect on pig fertility could be well-controlled by vaccination. However, at the beginning of the third millennium, field observations raised concerns about the effectiveness of the available vaccines against newly emerging strains. Subsequent investigations radically changed our view on the evolution and immunology of PPV, revealing that the virus is much more diverse than it was earlier anticipated, and that some of the “new” highly virulent isolates cannot be neutralized effectively by antisera raised against “old” PPV vaccine strains. These findings revitalized PPV research that led to significant advancements in the understanding of early and late viral processes during PPV infection. Our review summarizes the recent results of PPV research and aims to give a comprehensive update on the present understanding of PPV biology. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessReview Human Protoparvoviruses
Viruses 2017, 9(11), 354; https://doi.org/10.3390/v9110354
Received: 31 October 2017 / Revised: 17 November 2017 / Accepted: 19 November 2017 / Published: 22 November 2017
Cited by 4 | PDF Full-text (1567 KB) | HTML Full-text | XML Full-text
Abstract
Next-generation sequencing and metagenomics have revolutionized the discovery of novel viruses. In recent years, three novel protoparvoviruses have been discovered in fecal samples of humans: bufavirus (BuV) in 2012, tusavirus (TuV) in 2014, and cutavirus (CuV) in 2016. BuV has since been studied
[...] Read more.
Next-generation sequencing and metagenomics have revolutionized the discovery of novel viruses. In recent years, three novel protoparvoviruses have been discovered in fecal samples of humans: bufavirus (BuV) in 2012, tusavirus (TuV) in 2014, and cutavirus (CuV) in 2016. BuV has since been studied the most, disclosing three genotypes that also represent serotypes. Besides one nasal sample, BuV DNA has been found exclusively in diarrheal feces, but not in non-diarrheal feces, suggesting a causal relationship. According to both geno- and seroprevalences, BuV appears to be the most common of the three novel protoparvoviruses, whereas TuV DNA has been found in only a single fecal sample, with antibody detection being equally rare. Moreover, the TuV sequence is closer to those of non-human protoparvoviruses, and so the evidence of TuV being a human virus is thus far insufficient. Interestingly, besides in feces, CuV has also been detected in skin biopsies of patients with cutaneous T-cell lymphoma and a patient with melanoma, while all other skin samples have tested PCR negative. Even if preliminary disease associations exist, the full etiological roles of these viruses in human disease are yet to be resolved. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessReview Protoparvovirus Interactions with the Cellular DNA Damage Response
Viruses 2017, 9(11), 323; https://doi.org/10.3390/v9110323
Received: 22 September 2017 / Revised: 16 October 2017 / Accepted: 23 October 2017 / Published: 31 October 2017
Cited by 1 | PDF Full-text (813 KB) | HTML Full-text | XML Full-text
Abstract
Protoparvoviruses are simple single-stranded DNA viruses that infect many animal species. The protoparvovirus minute virus of mice (MVM) infects murine and transformed human cells provoking a sustained DNA damage response (DDR). This DDR is dependent on signaling by the ATM kinase and leads
[...] Read more.
Protoparvoviruses are simple single-stranded DNA viruses that infect many animal species. The protoparvovirus minute virus of mice (MVM) infects murine and transformed human cells provoking a sustained DNA damage response (DDR). This DDR is dependent on signaling by the ATM kinase and leads to a prolonged pre-mitotic cell cycle block that features the inactivation of ATR-kinase mediated signaling, proteasome-targeted degradation of p21, and inhibition of cyclin B1 expression. This review explores how protoparvoviruses, and specifically MVM, co-opt the common mechanisms regulating the DDR and cell cycle progression in order to prepare the host nuclear environment for productive infection. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessReview Protoparvovirus Cell Entry
Viruses 2017, 9(11), 313; https://doi.org/10.3390/v9110313
Received: 9 October 2017 / Revised: 21 October 2017 / Accepted: 23 October 2017 / Published: 26 October 2017
Cited by 2 | PDF Full-text (3112 KB) | HTML Full-text | XML Full-text
Abstract
The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes important animal pathogens and reference molecular models for the entire family. Some virus members of the PtPV genus have arisen as promising tools to treat tumoral processes, as they exhibit marked oncotropism
[...] Read more.
The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes important animal pathogens and reference molecular models for the entire family. Some virus members of the PtPV genus have arisen as promising tools to treat tumoral processes, as they exhibit marked oncotropism and oncolytic activities while being nonpathogenic for humans. The PtPVs invade and replicate within the nucleus making extensive use of the transport, transcription and replication machineries of the host cells. In order to reach the nucleus, PtPVs need to cross over several intracellular barriers and traffic through different cell compartments, which limit their infection efficiency. In this review we summarize molecular interactions, capsid structural transitions and hijacking of cellular processes, by which the PtPVs enter and deliver their single-stranded DNA genome into the host cell nucleus. Understanding mechanisms that govern the complex PtPV entry will be instrumental in developing approaches to boost their anticancer therapeutic potential and improving their safety profile. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessReview Protoparvovirus Knocking at the Nuclear Door
Viruses 2017, 9(10), 286; https://doi.org/10.3390/v9100286
Received: 5 September 2017 / Revised: 28 September 2017 / Accepted: 29 September 2017 / Published: 2 October 2017
Cited by 1 | PDF Full-text (463 KB) | HTML Full-text | XML Full-text
Abstract
Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the
[...] Read more.
Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural changes in the nuclear envelope, and is completed by intranuclear disassembly of capsids and chromatinization of the viral genome. This review discusses the nuclear import strategies of protoparvoviruses and describes its dynamics comprising active and passive movement, and directed and diffusive motion of capsids in the molecularly crowded environment of the cell. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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