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Pathogens
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The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics
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The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Vaccines and Therapeutic Developments".

Deadline for manuscript submissions: closed (1 December 2023) | Viewed by 29074

Special Issue Editors

Dr. Assia Angelova

E-Mail Website
Guest Editor
Clinical Cooperation Unit Virotherapy, German Cancer Research Center, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
Interests: parvoviruses; oncolytic viruses; cancer; cancer virotherapy; cancer viroimmunotherapy
Prof. Dr. Jean Rommelaere

E-Mail Website
Guest Editor
Clinical Cooperation Unit Virotherapy, German Cancer Research Center, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
Interests: parvoviruses; oncolytic viruses; cancer; cancer virotherapy; cancer viroimmunotherapy

Special Issue Information

Dear Colleagues,

Parvoviridae is a family of small (23–28 nm), non-enveloped viruses with an icosahedral capsid, which encloses a linear single-stranded 4-6 kb DNA genome flanked on both ends by short terminal hairpins. The family includes three subfamilies, twenty-three genera, and more than a hundred virus species. Notably, some of these viruses are animal or human pathogens, while others are used for gene therapy and oncolytic virus therapy purposes. This Special Issue of Pathogens aims at bringing together original research and review articles to provide the readers with a comprehensive picture of the multifaceted role of Parvoviridae in both disease induction and treatment. Recent discoveries, current state of the art, challenges, and prospects are discussed, with a particular focus on parvovirus newly identified associations with disease and exciting applications to the therapy of genetic disorders, including cancer.

Dr. Assia Angelova
Prof. Dr. Jean Rommelaere
Guest Editors

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Keywords

  • parvoviridae
  • gene therapy
  • oncolytic virus therapy
  • pathogenicity
  • genetic disorders

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Published Papers (6 papers)

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Research

Jump to: Review

30 pages, 13078 KiB  
Article
Oncolytic Rodent Protoparvoviruses Evade a TLR- and RLR-Independent Antiviral Response in Transformed Cells
by Assia Angelova, Kristina Pierrard, Claudia N. Detje, Estelle Santiago, Annabel Grewenig, Jürg P. F. Nüesch, Ulrich Kalinke, Guy Ungerechts, Jean Rommelaere and Laurent Daeffler
Pathogens 2023, 12(4), 607; https://doi.org/10.3390/pathogens12040607 - 17 Apr 2023
Cited by 4 | Viewed by 2213
Abstract
The oncolytic rodent protoparvoviruses (PVs) minute virus of mice (MVMp) and H-1 parvovirus (H-1PV) are promising cancer viro-immunotherapy candidates capable of both exhibiting direct oncolytic activities and inducing anticancer immune responses (AIRs). Type-I interferon (IFN) production is instrumental for the activation of an [...] Read more.
The oncolytic rodent protoparvoviruses (PVs) minute virus of mice (MVMp) and H-1 parvovirus (H-1PV) are promising cancer viro-immunotherapy candidates capable of both exhibiting direct oncolytic activities and inducing anticancer immune responses (AIRs). Type-I interferon (IFN) production is instrumental for the activation of an efficient AIR. The present study aims at characterizing the molecular mechanisms underlying PV modulation of IFN induction in host cells. MVMp and H-1PV triggered IFN production in semi-permissive normal mouse embryonic fibroblasts (MEFs) and human peripheral blood mononuclear cells (PBMCs), but not in permissive transformed/tumor cells. IFN production triggered by MVMp in primary MEFs required PV replication and was independent of the pattern recognition receptors (PRRs) Toll-like (TLR) and RIG-like (RLR) receptors. PV infection of (semi-)permissive cells, whether transformed or not, led to nuclear translocation of the transcription factors NFĸB and IRF3, hallmarks of PRR signaling activation. Further evidence showed that PV replication in (semi-)permissive cells resulted in nuclear accumulation of dsRNAs capable of activating mitochondrial antiviral signaling (MAVS)-dependent cytosolic RLR signaling upon transfection into naïve cells. This PRR signaling was aborted in PV-infected neoplastic cells, in which no IFN production was detected. Furthermore, MEF immortalization was sufficient to strongly reduce PV-induced IFN production. Pre-infection of transformed/tumor but not of normal cells with MVMp or H-1PV prevented IFN production by classical RLR ligands. Altogether, our data indicate that natural rodent PVs regulate the antiviral innate immune machinery in infected host cells through a complex mechanism. In particular, while rodent PV replication in (semi-)permissive cells engages a TLR-/RLR-independent PRR pathway, in transformed/tumor cells this process is arrested prior to IFN production. This virus-triggered evasion mechanism involves a viral factor(s), which exert(s) an inhibitory action on IFN production, particularly in transformed/tumor cells. These findings pave the way for the development of second-generation PVs that are defective in this evasion mechanism and therefore endowed with increased immunostimulatory potential through their ability to induce IFN production in infected tumor cells. Full article
(This article belongs to the Special Issue The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics)
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7 pages, 366 KiB  
Article
Primate Erythroparvovirus 1 Infection in Patients with Hematological Disorders
by Stefka Krumova, Ivona Andonova, Radostina Stefanova, Polina Miteva, Galina Nenkova and Judith M. Hübschen
Pathogens 2022, 11(5), 497; https://doi.org/10.3390/pathogens11050497 - 21 Apr 2022
Viewed by 2501
Abstract
Primate erythroparvovirus 1, commonly referred to as Parvovirus B19 (B19V), is a DNA virus that normally results in a mild childhood infection called “erythema infectiosum”. Besides respiratory spread, B19V can also be transmitted through transfusions, which may result in persistent anemia in immunodeficient [...] Read more.
Primate erythroparvovirus 1, commonly referred to as Parvovirus B19 (B19V), is a DNA virus that normally results in a mild childhood infection called “erythema infectiosum”. Besides respiratory spread, B19V can also be transmitted through transfusions, which may result in persistent anemia in immunodeficient hosts. Dialysis patients often face acute or chronic anemia after infection with B19V. Here, we describe the laboratory investigation of 21 patients with hematological disorders for B19V infections. B19V DNA was detected in 13 (62%) of them, with specific IgM antibodies in three of the DNA positives. All 13 patients received treatment and were laboratory-monitored over a period of one year. In only two patients (a 14-year-old child with a kidney transplantation and a 39-year-old patient with aplastic anemia), markers of recent B19V infection were still detectable in follow-up samples. For four B19V DNA positive samples, short sequences could be obtained, which clustered with genotype 1a reference strains. Our findings suggest that all cases of hematological disorders should be examined for specific B19V antibodies and DNA for accurate diagnosis and appropriate patient management. Full article
(This article belongs to the Special Issue The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics)
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20 pages, 3916 KiB  
Article
Generation and Validation of Monoclonal Antibodies Suitable for Detecting and Monitoring Parvovirus Infections
by Claudia Tessmer, Claudia Plotzky, Jana Fees, Hendrik Welsch, Rebecca Eudenbach, Martin Faber, Alicia Simón, Assia Angelova, Jean Rommelaere, Ilse Hofmann and Jürg P. F. Nüesch
Pathogens 2022, 11(2), 208; https://doi.org/10.3390/pathogens11020208 - 4 Feb 2022
Cited by 1 | Viewed by 2213
Abstract
For many applications it is necessary to detect target proteins in living cells. This is particularly the case when monitoring viral infections, in which the presence (or absence) of distinct target polypeptides potentially provides vital information about the pathology caused by the agent. [...] Read more.
For many applications it is necessary to detect target proteins in living cells. This is particularly the case when monitoring viral infections, in which the presence (or absence) of distinct target polypeptides potentially provides vital information about the pathology caused by the agent. To obtain suitable tools with which to monitor parvoviral infections, we thus generated monoclonal antibodies (mAbs) in order to detect the major non-structural protein NS1 in the intracellular environment and tested them for sensitivity and specificity, as well as for cross-reactivity towards related species. Using different immunogens and screening approaches based on indirect immunofluorescence, we describe here a panel of mAbs suitable for monitoring active infections with various parvovirus species by targeting the major non-structural protein NS1. In addition to mAbs detecting the NS1 of parvovirus H-1 (H-1PV) (belonging to the Rodent protoparvovirus 1 species, which is currently under validation as an anti-cancer agent), we generated tools with which to monitor infections by human cutavirus (CuV) and B19 virus (B19V) (belonging to the Primate protoparvovirus 3 and the Primate erythroparvovirus 1 species, respectively, which were both found to persistently infect human tissues). As well as mAbs able to detect NS1 from a broad range of parvoviruses, we obtained entities specific for either (distinct) members of the Rodent protoparvovirus 1 species, human CuV, or human B19V. Full article
(This article belongs to the Special Issue The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics)
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Review

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13 pages, 618 KiB  
Review
Transcriptional Targeting Approaches in Cardiac Gene Transfer Using AAV Vectors
by Lena C. Schröder, Derk Frank and Oliver J. Müller
Pathogens 2023, 12(11), 1301; https://doi.org/10.3390/pathogens12111301 - 30 Oct 2023
Cited by 3 | Viewed by 2108
Abstract
Cardiac-targeted transgene delivery offers new treatment opportunities for cardiovascular diseases, which massively contribute to global mortality. Restricted gene transfer to cardiac tissue might protect extracardiac organs from potential side-effects. This could be mediated by using cis-regulatory elements, including promoters and enhancers that act [...] Read more.
Cardiac-targeted transgene delivery offers new treatment opportunities for cardiovascular diseases, which massively contribute to global mortality. Restricted gene transfer to cardiac tissue might protect extracardiac organs from potential side-effects. This could be mediated by using cis-regulatory elements, including promoters and enhancers that act on the transcriptional level. Here, we discuss examples of tissue-specific promoters for targeted transcription in myocytes, cardiomyocytes, and chamber-specific cardiomyocytes. Some promotors are induced at pathological states, suggesting a potential use as “induction-by-disease switches” in gene therapy. Recent developments have resulted in the identification of novel enhancer-elements that could further pave the way for future refinement of transcriptional targeting, for example, into the cardiac conduction system. Full article
(This article belongs to the Special Issue The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics)
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14 pages, 1128 KiB  
Review
Therapeutic Potential of Engineered Virus-like Particles of Parvovirus B19
by Ignacio Sánchez-Moguel, Carmina Montiel and Ismael Bustos-Jaimes
Pathogens 2023, 12(8), 1007; https://doi.org/10.3390/pathogens12081007 - 2 Aug 2023
Cited by 2 | Viewed by 1942
Abstract
Virus-like particles (VLPs) comprise one or many structural components of virions, except their genetic material. Thus, VLPs keep their structural properties of cellular recognition while being non-infectious. VLPs of Parvovirus B19 (B19V) can be produced by the heterologous expression of their structural proteins [...] Read more.
Virus-like particles (VLPs) comprise one or many structural components of virions, except their genetic material. Thus, VLPs keep their structural properties of cellular recognition while being non-infectious. VLPs of Parvovirus B19 (B19V) can be produced by the heterologous expression of their structural proteins VP1 and VP2 in bacteria. These proteins are purified under denaturing conditions, refolded, and assembled into VLPs. Moreover, chimeric forms of VP2 have been constructed to harbor peptides or functional proteins on the surface of the particles without dropping their competence to form VLPs, serving as presenting nanoparticles. The in-vitro assembly approach offers exciting possibilities for the composition of VLPs, as more than one chimeric form of VP2 can be included in the assembly stage, producing multifunctional VLPs. Here, the heterologous expression and in-vitro assembly of B19V structural proteins and their chimeras are reviewed. Considerations for the engineering of the structural proteins of B19V are also discussed. Finally, the construction of multifunctional VLPs and their future potential as innovative medical tools are examined. Full article
(This article belongs to the Special Issue The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics)
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30 pages, 1284 KiB  
Review
Fantastic AAV Gene Therapy Vectors and How to Find Them—Random Diversification, Rational Design and Machine Learning
by Jonas Becker, Julia Fakhiri and Dirk Grimm
Pathogens 2022, 11(7), 756; https://doi.org/10.3390/pathogens11070756 - 3 Jul 2022
Cited by 44 | Viewed by 16127
Abstract
Parvoviruses are a diverse family of small, non-enveloped DNA viruses that infect a wide variety of species, tissues and cell types. For over half a century, their intriguing biology and pathophysiology has fueled intensive research aimed at dissecting the underlying viral and cellular [...] Read more.
Parvoviruses are a diverse family of small, non-enveloped DNA viruses that infect a wide variety of species, tissues and cell types. For over half a century, their intriguing biology and pathophysiology has fueled intensive research aimed at dissecting the underlying viral and cellular mechanisms. Concurrently, their broad host specificity (tropism) has motivated efforts to develop parvoviruses as gene delivery vectors for human cancer or gene therapy applications. While the sum of preclinical and clinical data consistently demonstrates the great potential of these vectors, these findings also illustrate the importance of enhancing and restricting in vivo transgene expression in desired cell types. To this end, major progress has been made especially with vectors based on Adeno-associated virus (AAV), whose capsid is highly amenable to bioengineering, repurposing and expansion of its natural tropism. Here, we provide an overview of the state-of-the-art approaches to create new AAV variants with higher specificity and efficiency of gene transfer in on-target cells. We first review traditional and novel directed evolution approaches, including high-throughput screening of AAV capsid libraries. Next, we discuss programmable receptor-mediated targeting with a focus on two recent technologies that utilize high-affinity binders. Finally, we highlight one of the latest stratagems for rational AAV vector characterization and optimization, namely, machine learning, which promises to facilitate and accelerate the identification of next-generation, safe and precise gene delivery vehicles. Full article
(This article belongs to the Special Issue The Multifaceted Parvoviridae Family: From Pathogens to Therapeutics)
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