Advances in Parvovirus Research 2022

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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 42478

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Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
Interests: parvovirus B19; virus–cell interactions; viral infections; recombinant viruses; virological diagnosis; antiviral strategies
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Special Issue Information

Dear Colleagues,

This Special Issue on ‘Advances in Parvovirus Research 2022’ continues the series dedicated to research on viruses belonging to the Parvoviridae family, following the issues “New Insights into Parvovirus Research” (https://www.mdpi.com/journal/viruses/special_issues/Parvovirus) and “Advances in Parvovirus Research 2020” (https://www.mdpi.com/journal/viruses/special_issues/parvovirus_2020).

The aim of this Special Issue is to continue to offer a dedicated opportunity for collecting the newest contributions in the field of parvovirus research, providing new insights and addressing research on unresolved issues. Evolution, structural biology, viral replication, virus–host interaction, pathogenesis and immunity, clinical virology of medical and veterinarian relevance, gene therapy, viral oncotherapy, and novel antiviral strategies are a just selection of topics relevant to research in the field, which can be contributed to this Special Issue.

The Special Issue is associated with the conference “XVIII International Parvovirus Workshop”, which will now be taking place in Rimini, Italy, in June 2022, as an on-site event. The international workshops dedicated to parvoviruses, first held in 1985, are events strictly centered on all aspects of parvovirus research and provide excellent opportunities to focus on research topics in this area. Symposium participants, as well as all researchers working in the field, are cordially invited to contribute original research papers or propose reviews to this Special Issue of Viruses. For further information, visit the dedicated website: https://www.parvovirusworkshop2022.org/

Dr. Giorgio Gallinella
Guest Editor

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Keywords

  • parvovirus evolution
  • parvovirus structure
  • parvovirus genetics
  • parvovirus–host interactions
  • parvovirus pathogenesis and immunity
  • parvovirus oncolytic therapy
  • parvovirus viral vectors
  • antiviral strategies

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Published Papers (18 papers)

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15 pages, 3357 KiB  
Article
Not Asian Anymore: Reconstruction of the History, Evolution, and Dispersal of the “Asian” Lineage of CPV-2c
by Giovanni Franzo, Francesco Mira, Giorgia Schirò and Marta Canuti
Viruses 2023, 15(9), 1962; https://doi.org/10.3390/v15091962 - 20 Sep 2023
Cited by 3 | Viewed by 1245
Abstract
Variability has been one of the hallmarks of canine parvovirus type 2 (CPV-2) since its discovery, and several lineages and antigenic variants have emerged. Among these, a group of viruses commonly called Asian CPV-2c has recently been reported with increasing frequency in different [...] Read more.
Variability has been one of the hallmarks of canine parvovirus type 2 (CPV-2) since its discovery, and several lineages and antigenic variants have emerged. Among these, a group of viruses commonly called Asian CPV-2c has recently been reported with increasing frequency in different regions. Currently, its global epidemiology and evolution are essentially unknown. The present work deals with this information gap by evaluating, via sequence, phylodynamic, and phylogeographic analyses, all the complete coding sequences of strains classified as Asian CPV-2c based on a combination of amino acid markers and phylogenetic analysis. After its estimated origin around 2008, this lineage circulated undetected in Asia until approximately 2012, when an expansion in viral population size and geographical distribution occurred, involving Africa, Europe, and North America. Asia was predicted to be the main nucleus of viral dispersal, leading to multiple introduction events in other continents/countries, where infection establishment, persistence, and rapid evolution occurred. Although the dog is the main host, other non-canine species were also involved, demonstrating the host plasticity of this lineage. Finally, although most of the strains showed an amino acid motif considered characteristic of this lineage, several exceptions were observed, potentially due to convergent evolution or reversion phenomena. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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13 pages, 28389 KiB  
Article
Structural Characterization of Canine Minute Virus, Rat and Porcine Bocavirus
by Michael Velez, Mario Mietzsch, Jane Hsi, Logan Bell, Paul Chipman, Xiaofeng Fu and Robert McKenna
Viruses 2023, 15(9), 1799; https://doi.org/10.3390/v15091799 - 24 Aug 2023
Cited by 1 | Viewed by 1415
Abstract
Bocaparvovirus is an expansive genus of the Parvovirinae, with a wide range of vertebrate hosts. This study investigates Canine minute virus (CnMV), Rat bocavirus (RBoV), and Porcine bocavirus 1 (PBoV1). Both CnMV and PBoV1 have been found in gastrointestinal infections in their [...] Read more.
Bocaparvovirus is an expansive genus of the Parvovirinae, with a wide range of vertebrate hosts. This study investigates Canine minute virus (CnMV), Rat bocavirus (RBoV), and Porcine bocavirus 1 (PBoV1). Both CnMV and PBoV1 have been found in gastrointestinal infections in their respective hosts, with CnMV responsible for spontaneous abortions in dogs, while PBoV has been associated with encephalomyelitis in piglets. The pathogenicity of the recently identified RBoV is currently unknown. To initiate the characterization of these viruses, their capsids structures were determined by cryo-electron microscopy at resolutions ranging from 2.3 to 2.7 Å. Compared to other parvoviruses, the CnMV, PBoV1, and RBoV capsids showed conserved features, such as the channel at the fivefold symmetry axis. However, major differences were observed at the two- and threefold axes. While CnMV displays prominent threefold protrusions, the same region is more recessed in PBoV1 and RBoV. Furthermore, the typical twofold axis depression of parvoviral capsids is absent in CnMV or very small in PBoV and RBoV. These capsid structures extend the structural portfolio for the Bocaparvovirus genus and will allow future characterization of these pathogens on a molecular level. This is important, as no antivirals or vaccines exist for these viruses. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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15 pages, 2026 KiB  
Article
Antiviral Activity of an Endogenous Parvoviral Element
by Angelica Bravo, Leandro Fernández-García, Rodrigo Ibarra-Karmy, Gonzalo A. Mardones, Luis Mercado, Fernando J. Bustos, Robert J. Gifford and Gloria Arriagada
Viruses 2023, 15(7), 1420; https://doi.org/10.3390/v15071420 - 23 Jun 2023
Cited by 1 | Viewed by 1536
Abstract
Endogenous viral elements (EVEs) are genomic DNA sequences derived from viruses. Some EVEs have open reading frames (ORFs) that can express proteins with physiological roles in their host. Furthermore, some EVEs exhibit a protective role against exogenous viral infection in their host. Endogenous [...] Read more.
Endogenous viral elements (EVEs) are genomic DNA sequences derived from viruses. Some EVEs have open reading frames (ORFs) that can express proteins with physiological roles in their host. Furthermore, some EVEs exhibit a protective role against exogenous viral infection in their host. Endogenous parvoviral elements (EPVs) are highly represented in mammalian genomes, and although some of them contain ORFs, their function is unknown. We have shown that the locus EPV-Dependo.43-ODegus, an EPV with an intact ORF, is transcribed in Octodon degus (degu). Here we examine the antiviral activity of the protein encoded in this EPV, named DeRep. DeRep was produced in bacteria and used to generate antibodies that recognize DeRep in western blots of degu tissue. To test if DeRep could protect against exogenous parvovirus, we challenged cells with the minute virus of mice (MVM), a model autonomous parvovirus. We observed that MVM protein expression, DNA damage induced by replication, viral DNA, and cytopathic effects are reduced when DeRep is expressed in cells. The results of this study demonstrate that DeRep is expressed in degu and can inhibit parvovirus replication. This is the first time that an EPV has been shown to have antiviral activity against an exogenous virus. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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15 pages, 2263 KiB  
Article
The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling
by Clairine I. S. Larsen and Kinjal Majumder
Viruses 2023, 15(6), 1243; https://doi.org/10.3390/v15061243 - 25 May 2023
Cited by 2 | Viewed by 1750
Abstract
Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvoviridae family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral [...] Read more.
Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvoviridae family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 localization to cellular DDR sites is independent of ATM or DNA-PK signaling but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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14 pages, 2549 KiB  
Article
Next Generation Sequencing for the Analysis of Parvovirus B19 Genomic Diversity
by Federica Bichicchi, Niccolò Guglietta, Arthur Daniel Rocha Alves, Erika Fasano, Elisabetta Manaresi, Gloria Bua and Giorgio Gallinella
Viruses 2023, 15(1), 217; https://doi.org/10.3390/v15010217 - 12 Jan 2023
Cited by 1 | Viewed by 1911
Abstract
Parvovirus B19 (B19V) is a ssDNA human virus, responsible for an ample range of clinical manifestations. Sequencing of B19V DNA from clinical samples is frequently reported in the literature to assign genotype (genotypes 1–3) and for finer molecular epidemiological tracing. The increasing availability [...] Read more.
Parvovirus B19 (B19V) is a ssDNA human virus, responsible for an ample range of clinical manifestations. Sequencing of B19V DNA from clinical samples is frequently reported in the literature to assign genotype (genotypes 1–3) and for finer molecular epidemiological tracing. The increasing availability of Next Generation Sequencing (NGS) with its depth of coverage potentially yields information on intrinsic sequence heterogeneity; however, integration of this information in analysis of sequence variation is not routinely obtained. The present work investigated genomic sequence heterogeneity within and between B19V isolates by application of NGS techniques, and by the development of a novel dedicated bioinformatic tool and analysis pipeline, yielding information on two newly defined parameters. The first, α-diversity, is a measure of the amount and distribution of position-specific, normalised Shannon Entropy, as a measure of intra-sample sequence heterogeneity. The second, σ-diversity, is a measure of the amount of inter-sample sequence heterogeneity, also incorporating information on α-diversity. Based on these indexes, further cluster analysis can be performed. A set of 24 high-titre viraemic samples was investigated. Of these, 23 samples were genotype 1 and one sample was genotype 2. Genotype 1 isolates showed low α-diversity values, with only a few samples showing distinct position-specific polymorphisms; a few genetically related clusters emerged when analysing inter-sample distances, correlated to the year of isolation; the single genotype 2 isolate showed the highest α-diversity, even if not presenting polymorphisms, and was an evident outlier when analysing inter-sample distance. In conclusion, NGS analysis and the bioinformatic tool and pipeline developed and used in the present work can be considered effective tools for investigating sequence diversity, an observable parameter that can be incorporated into the quasispecies theory framework to yield a better insight into viral evolution dynamics. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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19 pages, 2092 KiB  
Article
Design and Characterization of Mutated Variants of the Oncotoxic Parvoviral Protein NS1
by Patrick Hauswirth, Philipp Graber, Katarzyna Buczak, Riccardo Vincenzo Mancuso, Susanne Heidi Schenk, Jürg P. F. Nüesch and Jörg Huwyler
Viruses 2023, 15(1), 209; https://doi.org/10.3390/v15010209 - 11 Jan 2023
Viewed by 2205
Abstract
Oncotoxic proteins such as the non-structural protein 1 (NS1), a constituent of the rodent parvovirus H1 (H1-PV), offer a novel approach for treatment of tumors that are refractory to other treatments. In the present study, mutated NS1 variants were designed and tested with [...] Read more.
Oncotoxic proteins such as the non-structural protein 1 (NS1), a constituent of the rodent parvovirus H1 (H1-PV), offer a novel approach for treatment of tumors that are refractory to other treatments. In the present study, mutated NS1 variants were designed and tested with respect to their oncotoxic potential in human hepatocellular carcinoma cell lines. We introduced single point mutations of previously described important residues of the wild-type NS1 protein and a deletion of 114 base pairs localized within the N-terminal domain of NS1. Cell-viability screening with HepG2 and Hep3B hepatocarcinoma cells transfected with the constructed NS1-mutants led to identification of the single-amino acid NS1-mutant NS1-T585E, which led to a 30% decrease in cell viability as compared to NS1 wildtype. Using proteomics analysis, we could identify new interaction partners and signaling pathways of NS1. We could thus identify new oncotoxic NS1 variants and gain insight into the modes of action of NS1, which is exclusively toxic to human cancer cells. Our in-vitro studies provide mechanistic explanations for the observed oncolytic effects. Expression of NS1 variants had no effect on cell viability in NS1 unresponsive control HepG2 cells or primary mouse hepatocytes. The availability of new NS1 variants in combination with a better understanding of their modes of action offers new possibilities for the design of innovative cancer treatment strategies. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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9 pages, 625 KiB  
Article
A Phylogeographic Analysis of Porcine Parvovirus 1 in Africa
by Giovanni Franzo, Habibata Lamouni Zerbo, Bruno Lalidia Ouoba, Adama Drabo Dji-Tombo, Marietou Guitti Kindo, Rasablaga Sawadogo, Jelly Chang’a, Stella Bitanyi, Aloyce Kamigwe, Charles Mayenga, Modou Moustapha Lo, Mbengué Ndiaye, Aminata Ba, Gaye Laye Diop, Iolanda Vieira Anahory, Lourenço P. Mapaco, Sara J. Achá, Valere Kouame Kouakou, Emmanuel Couacy-Hymann, Stephen G. Gacheru, Jacqueline K. Lichoti, Justus K. Kasivalu, Obadiah N. Njagi, Tirumala B. K. Settypalli, Giovanni Cattoli, Charles E. Lamien, Umberto Molini and William G. Dundonadd Show full author list remove Hide full author list
Viruses 2023, 15(1), 207; https://doi.org/10.3390/v15010207 - 11 Jan 2023
Cited by 4 | Viewed by 1517
Abstract
Porcine parvovirus 1 (PPV1) is recognized as a major cause of reproductive failure in pigs, leading to several clinical outcomes globally known as SMEDI. Despite being known since the late 1960s its circulation is still of relevance to swine producers. Additionally, the emergence [...] Read more.
Porcine parvovirus 1 (PPV1) is recognized as a major cause of reproductive failure in pigs, leading to several clinical outcomes globally known as SMEDI. Despite being known since the late 1960s its circulation is still of relevance to swine producers. Additionally, the emergence of variants such as the virulent 27a strain, for which lower protection induced by vaccines has been demonstrated, is of increasing concern. Even though constant monitoring of PPV1 using molecular epidemiological approaches is of pivotal importance, viral sequence data are scarce especially in low-income countries. To fill this gap, a collection of 71 partial VP2 sequences originating from eight African countries (Burkina Faso, Côte d’Ivoire, Kenya, Mozambique, Namibia, Nigeria, Senegal, and Tanzania) during the period 2011–2021 were analyzed within the context of global PPV1 variability. The observed pattern largely reflected what has been observed in high-income regions, i.e., 27a-like strains were more frequently detected than less virulent NADL-8-like strains. A phylogeographic analysis supported this observation, highlighting that the African scenario has been largely shaped by multiple PPV1 importation events from other continents, especially Europe and Asia. The existence of such an international movement coupled with the circulation of potential vaccine-escape variants requires the careful evaluation of the control strategies to prevent new strain introduction and persistence. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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11 pages, 1862 KiB  
Communication
Carnivore protoparvovirus 1 (CPV-2 and FPV) Circulating in Wild Carnivores and in Puppies Illegally Imported into North-Eastern Italy
by Stefania Leopardi, Adelaide Milani, Monia Cocchi, Marco Bregoli, Alessia Schivo, Sofia Leardini, Francesca Festa, Ambra Pastori, Gabrita de Zan, Federica Gobbo, Maria Serena Beato, Manlio Palei, Alessandro Bremini, Marie-Christin Rossmann, Paolo Zucca, Isabella Monne and Paola De Benedictis
Viruses 2022, 14(12), 2612; https://doi.org/10.3390/v14122612 - 23 Nov 2022
Cited by 5 | Viewed by 1781
Abstract
The illegal trade of animals poses several health issues to the global community, among which are the underestimated risk for spillover infection and the potential for an epizootic in both wildlife and domestic naïve populations. We herein describe the genetic and antigenic characterization [...] Read more.
The illegal trade of animals poses several health issues to the global community, among which are the underestimated risk for spillover infection and the potential for an epizootic in both wildlife and domestic naïve populations. We herein describe the genetic and antigenic characterization of viruses of the specie Carnivore protoparvovirus 1 detected at high prevalence in puppies illegally introduced in North Eastern Italy and compared them with those circulating in wild carnivores from the same area. We found evidence of a wide diversity of canine parvoviruses (CPV-2) belonging to different antigenic types in illegally imported pups. In wildlife, we found a high circulation of feline parvovirus (FPV) in golden jackals and badgers, whereas CPV-2 was observed in one wolf only. Although supporting a possible spillover event, the low representation of wolf samples in the present study prevented us from inferring the origin, prevalence and viral diversity of the viruses circulating in this species. Therefore, we suggest performing more thorough investigations before excluding endemic CPV-2 circulation in this species. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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16 pages, 4648 KiB  
Article
Capsid Structure of Aleutian Mink Disease Virus and Human Parvovirus 4: New Faces in the Parvovirus Family Portrait
by Renuk Lakshmanan, Mario Mietzsch, Alberto Jimenez Ybargollin, Paul Chipman, Xiaofeng Fu, Jianming Qiu, Maria Söderlund-Venermo and Robert McKenna
Viruses 2022, 14(10), 2219; https://doi.org/10.3390/v14102219 - 9 Oct 2022
Cited by 2 | Viewed by 2469
Abstract
Parvoviruses are small, single-stranded DNA viruses with non-enveloped capsids. Determining the capsid structures provides a framework for annotating regions important to the viral life cycle. Aleutian mink disease virus (AMDV), a pathogen in minks, and human parvovirus 4 (PARV4), infecting humans, are parvoviruses [...] Read more.
Parvoviruses are small, single-stranded DNA viruses with non-enveloped capsids. Determining the capsid structures provides a framework for annotating regions important to the viral life cycle. Aleutian mink disease virus (AMDV), a pathogen in minks, and human parvovirus 4 (PARV4), infecting humans, are parvoviruses belonging to the genera Amdoparvovirus and Tetraparvovirus, respectively. While Aleutian mink disease caused by AMDV is a major threat to mink farming, no clear clinical manifestations have been established following infection with PARV4 in humans. Here, the capsid structures of AMDV and PARV4 were determined via cryo-electron microscopy at 2.37 and 3.12 Å resolutions, respectively. Despite low amino acid sequence identities (10–30%) both viruses share the icosahedral nature of parvovirus capsids, with 60 viral proteins (VPs) assembling the capsid via two-, three-, and five-fold symmetry VP-related interactions, but display major structural variabilities in the surface loops when the capsid structures are superposed onto other parvoviruses. The capsid structures of AMDV and PARV4 will add to current knowledge of the structural platform for parvoviruses and permit future functional annotation of these viruses, which will help in understanding their infection mechanisms at a molecular level for the development of diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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12 pages, 3481 KiB  
Article
Self-Assembly of Porcine Parvovirus Virus-like Particles and Their Application in Serological Assay
by Yanfei Gao, Haiwei Wang, Shanghui Wang, Mingxia Sun, Zheng Fang, Xinran Liu, Xuehui Cai and Yabin Tu
Viruses 2022, 14(8), 1828; https://doi.org/10.3390/v14081828 - 20 Aug 2022
Viewed by 2377
Abstract
Porcine parvovirus (PPV) is widely prevalent in pig farms. PPV is closely related to porcine respiratory disease complex (PRDC) and porcine circovirus disease (PCVD), which seriously threatens the healthy development of the pig industry. Although commercial antibody detection kits are available, they are [...] Read more.
Porcine parvovirus (PPV) is widely prevalent in pig farms. PPV is closely related to porcine respiratory disease complex (PRDC) and porcine circovirus disease (PCVD), which seriously threatens the healthy development of the pig industry. Although commercial antibody detection kits are available, they are expensive and unsuitable for large-scale clinical practice. Here, a soluble VP2 protein of PPV is efficiently expressed in the E. coli expression system. The VP2 protein can be self-assembled into virus-like particles (VLPs) in vitro. After multiple steps of chromatography purification, PPV-VLPs with a purity of about 95% were obtained. An indirect, enzyme-linked immunosorbent assay (I-ELISA), comparable to a commercial PPV kit, was developed based on the purified PPV-VLPs and was used to detect 487 clinical pig serum samples. The results showed that the I-ELISA is a simple, cost-effective, and efficient method for the diagnosis of clinical pig serum and plasma samples. In summary, high-purity, tag-free PPV-VLPs were prepared, and the established VLP-based I-ELISA is of great significance for the sero-monitoring of antibodies against PPV. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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13 pages, 3802 KiB  
Article
Robust AAV Genotyping Based on Genetic Distances in Rep Gene That Are Maintained by Ubiquitous Recombination
by Marina I. Beloukhova, Alexander N. Lukashev, Pavel Y. Volchkov, Andrey A. Zamyatnin, Jr. and Andrei A. Deviatkin
Viruses 2022, 14(5), 1038; https://doi.org/10.3390/v14051038 - 13 May 2022
Cited by 3 | Viewed by 2880
Abstract
Adeno-associated viruses (AAVs) are a convenient tool for gene therapy delivery. According to the current classification, they are divided into the species AAV A and AAV B within the genus Dependoparvovirus. Historically AAVs were also subdivided on the intraspecies level into 13 serotypes, [...] Read more.
Adeno-associated viruses (AAVs) are a convenient tool for gene therapy delivery. According to the current classification, they are divided into the species AAV A and AAV B within the genus Dependoparvovirus. Historically AAVs were also subdivided on the intraspecies level into 13 serotypes, which differ in tissue tropism and targeted gene delivery capacity. Serotype, however, is not a universal taxonomic category, and their assignment is not always robust. Cross-reactivity has been shown, indicating that classification could not rely on the results of serological tests alone. Moreover, since the isolation of AAV4, all subsequent AAVs were subdivided into serotypes based primarily on genetic differences and phylogenetic reconstructions. An increased interest in the use of AAV as a gene delivery tool justifies the need to improve the existing classification. Here, we suggest genotype-based AAV classification below the species level based on the rep gene. A robust threshold was established as 10% nt differences within the 1248 nt genome fragment, with 4 distinct AAV genotypes identified. This distinct sub-species structure is maintained by ubiquitous recombination within, but not between, rep genes of the suggested genotypes. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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25 pages, 8113 KiB  
Article
Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells
by Tiago Ferreira, Amit Kulkarni, Clemens Bretscher, Petr V. Nazarov, Jubayer A. Hossain, Lars A. R. Ystaas, Hrvoje Miletic, Ralph Röth, Beate Niesler and Antonio Marchini
Viruses 2022, 14(5), 1018; https://doi.org/10.3390/v14051018 - 11 May 2022
Cited by 8 | Viewed by 5754
Abstract
Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that [...] Read more.
Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of LGALS1, the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of LGALS1 into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that LGALS1 is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between LGALS1 transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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13 pages, 1965 KiB  
Article
Evaluation of Molecular Test for the Discrimination of “Naked” DNA from Infectious Parvovirus B19 Particles in Serum and Bone Marrow Samples
by Arthur Daniel Rocha Alves, Barbara Barbosa Langella, Mariana Magaldi de Souza Lima, Wagner Luís da Costa Nunes Pimentel Coelho, Rita de Cássia Nasser Cubel Garcia, Claudete Aparecida Araújo Cardoso, Renato Sergio Marchevsky, Marcelo Alves Pinto and Luciane Almeida Amado
Viruses 2022, 14(4), 843; https://doi.org/10.3390/v14040843 - 18 Apr 2022
Cited by 5 | Viewed by 2230
Abstract
Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of [...] Read more.
Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of B19V DNA does not necessarily imply that infectious virions are present. This study aimed to evaluate the method based on the Benzonase® treatment for differentiation between the infectious virions from “naked” DNA in serum and bone marrow (BM) samples to be useful for the B19V routine diagnosis. In addition, we estimated the period of viremia and DNAemia in the sera and bone marrow of nonhuman primates experimentally infected with B19V. Serum samples from ten patients and from four cynomolgus monkeys experimentally infected with B19V followed up for 60 days were used. Most of the human serum samples became negative after pretreatment; however, only decreased viral DNA loads were observed in four patients, indicating that these samples still contained the infectious virus. Reduced B19V DNA levels were observed in animals since 7th dpi. At approximately 45th dpi, B19V DNA levels were below 105 IU/mL after Benzonase® pretreatment, which was not a consequence of active B19V replication. The test based on Benzonase® pretreatment enabled the discrimination of “naked DNA” from B19V DNA encapsidated in virions. Therefore, this test can be used to clarify the role of B19V as an etiological agent associated with atypical clinical manifestations. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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16 pages, 2779 KiB  
Article
A Conserved Receptor-Binding Domain in the VP1u of Primate Erythroparvoviruses Determines the Marked Tropism for Erythroid Cells
by Cornelia Bircher, Jan Bieri, Ruben Assaraf, Remo Leisi and Carlos Ros
Viruses 2022, 14(2), 420; https://doi.org/10.3390/v14020420 - 17 Feb 2022
Cited by 2 | Viewed by 2588
Abstract
Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central [...] Read more.
Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central role of VP1uR in the virus tropism, we sought to investigate its expression profile in multiple cell types. To this end, we established a PP7 bacteriophage-VP1u bioconjugate, sharing the size and VP1u composition of native B19V capsids. The suitability of the PP7-VP1u construct as a specific and sensitive VP1uR expression marker was validated in competition assays with B19V and recombinant VP1u. VP1uR expression was exclusively detected in erythroid cells and cells reprogrammed towards the erythroid lineage. Sequence alignment and in silico protein structure prediction of the N-terminal of VP1u (N-VP1u) from B19V and other primate erythroparvoviruses (simian, rhesus, and pig-tailed) revealed a similar structure characterized by a fold of three or four α-helices. Functional studies with simian parvovirus confirmed the presence of a conserved RBD in the N-VP1u, mediating virus internalization into human erythroid cells. In summary, this study confirms the exclusive association of VP1uR expression with cells of the erythroid lineage. The presence of an analogous RBD in the VP1u from non-human primate erythroparvoviruses emphasizes their parallel evolutionary trait and zoonotic potential. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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14 pages, 5932 KiB  
Article
A Functional Minigenome of Parvovirus B19
by Alessandro Reggiani, Andrea Avati, Francesca Valenti, Erika Fasano, Gloria Bua, Elisabetta Manaresi and Giorgio Gallinella
Viruses 2022, 14(1), 84; https://doi.org/10.3390/v14010084 - 4 Jan 2022
Cited by 2 | Viewed by 2480
Abstract
Parvovirus B19 (B19V) is a human pathogenic virus of clinical relevance, characterized by a selective tropism for erythroid progenitor cells in bone marrow. Relevant information on viral characteristics and lifecycle can be obtained from experiments involving engineered genetic systems in appropriate in vitro [...] Read more.
Parvovirus B19 (B19V) is a human pathogenic virus of clinical relevance, characterized by a selective tropism for erythroid progenitor cells in bone marrow. Relevant information on viral characteristics and lifecycle can be obtained from experiments involving engineered genetic systems in appropriate in vitro cellular models. Previously, a B19V genome of defined consensus sequence was designed, synthesized and cloned in a complete and functional form, able to replicate and produce infectious viral particles in a producer/amplifier cell system. Based on such a system, we have now designed and produced a derived B19V minigenome, reduced to a replicon unit. The genome terminal regions were maintained in a form able to sustain viral replication, while the internal region was clipped to include only the left-side genetic set, containing the coding sequence for the functional NS1 protein. Following transfection in UT7/EpoS1 cells, this minigenome still proved competent for replication, transcription and production of NS1 protein. Further, the B19V minigenome was able to complement B19-derived, NS1-defective genomes, restoring their ability to express viral capsid proteins. The B19V genome was thus engineered to yield a two-component system, with complementing functions, providing a valuable tool for studying viral expression and genetics, suitable to further engineering for purposes of translational research. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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26 pages, 504 KiB  
Conference Report
The XVIII International Parvovirus Workshop Rimini, Italy, 14–17 June 2022
by Giorgio Gallinella and Antonio Marchini
Viruses 2023, 15(10), 2129; https://doi.org/10.3390/v15102129 - 20 Oct 2023
Viewed by 1096
Abstract
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 [...] Read more.
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). Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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10 pages, 3088 KiB  
Case Report
Clinical Presentation of Parvovirus B19 Infection in Adults Living with HIV/AIDS: A Case Series
by Daniela P. Mendes-de-Almeida, Joanna Paes Barreto Bokel, Arthur Daniel Rocha Alves, Alexandre G. Vizzoni, Isabel Cristina Ferreira Tavares, Mayara Secco Torres Silva, Juliana dos Santos Barbosa Netto, Beatriz Gilda Jegerhorn Grinsztejn and Luciane Almeida Amado Leon
Viruses 2023, 15(5), 1124; https://doi.org/10.3390/v15051124 - 8 May 2023
Viewed by 2823
Abstract
Parvovirus B19 (B19V) infection varies clinically depending on the host’s immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and transient aplastic crisis in patients with immunosuppression or chronic hemolysis. We report three rare cases of Brazilian adults [...] Read more.
Parvovirus B19 (B19V) infection varies clinically depending on the host’s immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and transient aplastic crisis in patients with immunosuppression or chronic hemolysis. We report three rare cases of Brazilian adults living with human immunodeficiency virus (HIV) with B19V infection. All cases presented severe anemia and required red blood cell transfusions. The first patient had low CD4+ counts and was treated with intravenous immunoglobulin (IVIG). As he remained poorly adherent to antiretroviral therapy (ART), B19V detection persisted. The second patient had sudden pancytopenia despite being on ART with an undetectable HIV viral load. He had historically low CD4+ counts, fully responded to IVIG, and had undiagnosed hereditary spherocytosis. The third individual was recently diagnosed with HIV and tuberculosis (TB). One month after ART initiation, he was hospitalized with anemia aggravation and cholestatic hepatitis. An analysis of his serum revealed B19V DNA and anti-B19V IgG, corroborating bone marrow findings and a persistent B19V infection. The symptoms resolved and B19V became undetectable. In all cases, real time PCR was essential for diagnosing B19V. Our findings showed that adherence to ART was crucial to B19V clearance in HIV-patients and highlighted the importance of the early recognition of B19V disease in unexplained cytopenias. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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10 pages, 2424 KiB  
Brief Report
First Report of Skunk Amdoparvovirus (Species Carnivore amdoparvovirus 4) in Europe in a Captive Striped Skunk (Mephitis mephitis)
by Franziska K. Kaiser, Madeleine de le Roi, Wendy K. Jo, Ingo Gerhauser, Viktor Molnár, Albert D. M. E. Osterhaus, Wolfgang Baumgärtner and Martin Ludlow
Viruses 2023, 15(5), 1087; https://doi.org/10.3390/v15051087 - 28 Apr 2023
Viewed by 1341
Abstract
Skunk amdoparvovirus (Carnivore amdoparvovirus 4, SKAV) is closely related to Aleutian mink disease virus (AMDV) and circulates primarily in striped skunks (Mephitis mephitis) in North America. SKAV poses a threat to mustelid species due to reported isolated infections of [...] Read more.
Skunk amdoparvovirus (Carnivore amdoparvovirus 4, SKAV) is closely related to Aleutian mink disease virus (AMDV) and circulates primarily in striped skunks (Mephitis mephitis) in North America. SKAV poses a threat to mustelid species due to reported isolated infections of captive American mink (Neovison vison) in British Columbia, Canada. We detected SKAV in a captive striped skunk in a German zoo by metagenomic sequencing. The pathological findings are dominated by lymphoplasmacellular inflammation and reveal similarities to its relative Carnivore amdoparvovirus 1, the causative agent of Aleutian mink disease. Phylogenetic analysis of the whole genome demonstrated 94.80% nucleotide sequence identity to a sequence from Ontario, Canada. This study is the first case description of a SKAV infection outside of North America. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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