Research

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18 pages, 1980 KiB

Open AccessArticle

Molecular Investigation of Canine Parvovirus-2 (CPV-2) Outbreak in Nevis Island: Analysis of the Nearly Complete Genomes of CPV-2 Strains from the Caribbean Region

by Kerry Gainor, April Bowen, Pompei Bolfa, Andrea Peda, Yashpal S. Malik and Souvik Ghosh

Viruses 2021, 13(6), 1083; https://doi.org/10.3390/v13061083 - 06 Jun 2021

Cited by 9 | Viewed by 3435

Abstract

To date, there is a dearth of information on canine parvovirus-2 (CPV-2) from the Caribbean region. During August–October 2020, the veterinary clinic on the Caribbean island of Nevis reported 64 household dogs with CPV-2-like clinical signs (hemorrhagic/non-hemorrhagic diarrhea and vomiting), of which 27 [...] Read more.

To date, there is a dearth of information on canine parvovirus-2 (CPV-2) from the Caribbean region. During August–October 2020, the veterinary clinic on the Caribbean island of Nevis reported 64 household dogs with CPV-2-like clinical signs (hemorrhagic/non-hemorrhagic diarrhea and vomiting), of which 27 animals died. Rectal swabs/fecal samples were obtained from 43 dogs. A total of 39 of the 43 dogs tested positive for CPV-2 antigen and/or DNA, while 4 samples, negative for CPV-2 antigen, were not available for PCR. Among the 21 untested dogs, 15 had CPV-2 positive littermates. Analysis of the complete VP2 sequences of 32 strains identified new CPV-2a (CPV-2a with Ser297Ala in VP2) as the predominant CPV-2 on Nevis Island. Two nonsynonymous mutations, one rare (Asp373Asn) and the other uncommon (Ala262Thr), were observed in a few VP2 sequences. It was intriguing that new CPV-2a was associated with an outbreak of gastroenteritis on Nevis while found at low frequencies in sporadic cases of diarrhea on the neighboring island of St. Kitts. The nearly complete CPV-2 genomes (4 CPV-2 strains from St. Kitts and Nevis (SKN)) were reported for the first time from the Caribbean region. Eleven substitutions were found among the SKN genomes, which included nine synonymous substitutions, five of which have been rarely reported, and the two nonsynonymous substitutions. Phylogenetically, the SKN CPV-2 sequences formed a distinct cluster, with CPV-2b/USA/1998 strains constituting the nearest cluster. Our findings suggested that new CPV-2a is endemic in the region, with the potential to cause severe outbreaks, warranting further studies across the Caribbean Islands. Analysis of the SKN CPV-2 genomes corroborated the hypothesis that recurrent parallel evolution and reversion might play important roles in the evolution of CPV-2. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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17 pages, 10089 KiB

Open AccessArticle

Characterization of the GBoV1 Capsid and Its Antibody Interactions

by Jennifer Chun Yu, Mario Mietzsch, Amriti Singh, Alberto Jimenez Ybargollin, Shweta Kailasan, Paul Chipman, Nilakshee Bhattacharya, Julia Fakhiri, Dirk Grimm, Amit Kapoor, Indrė Kučinskaitė-Kodzė, Aurelija Žvirblienė, Maria Söderlund-Venermo, Robert McKenna and Mavis Agbandje-McKenna

Viruses 2021, 13(2), 330; https://doi.org/10.3390/v13020330 - 20 Feb 2021

Cited by 5 | Viewed by 3628

Abstract

Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better [...] Read more.

Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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15 pages, 17200 KiB

Open AccessArticle

Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features

by Mario Mietzsch, Ariana Jose, Paul Chipman, Nilakshee Bhattacharya, Nadia Daneshparvar, Robert McKenna and Mavis Agbandje-McKenna

Viruses 2021, 13(1), 101; https://doi.org/10.3390/v13010101 - 13 Jan 2021

Cited by 45 | Viewed by 8676

Abstract

The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, [...] Read more.

The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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16 pages, 3959 KiB

Open AccessArticle

Enhanced Cell-Based Detection of Parvovirus B19V Infectious Units According to Cell Cycle Status

by Céline Ducloux, Bruno You, Amandine Langelé, Olivier Goupille, Emmanuel Payen, Stany Chrétien and Zahra Kadri

Viruses 2020, 12(12), 1467; https://doi.org/10.3390/v12121467 - 18 Dec 2020

Cited by 2 | Viewed by 2697

Abstract

Human parvovirus B19 (B19V) causes various human diseases, ranging from childhood benign infection to arthropathies, severe anemia and fetal hydrops, depending on the health state and hematological status of the patient. To counteract B19V blood-borne contamination, evaluation of B19 DNA in plasma pools [...] Read more.

Human parvovirus B19 (B19V) causes various human diseases, ranging from childhood benign infection to arthropathies, severe anemia and fetal hydrops, depending on the health state and hematological status of the patient. To counteract B19V blood-borne contamination, evaluation of B19 DNA in plasma pools and viral inactivation/removal steps are performed, but nucleic acid testing does not correctly reflect B19V infectivity. There is currently no appropriate cellular model for detection of infectious units of B19V. We describe here an improved cell-based method for detecting B19V infectious units by evaluating its host transcription. We evaluated the ability of various cell lines to support B19V infection. Of all tested, UT7/Epo cell line, UT7/Epo-STI, showed the greatest sensitivity to B19 infection combined with ease of performance. We generated stable clones by limiting dilution on the UT7/Epo-STI cell line with graduated permissiveness for B19V and demonstrated a direct correlation between infectivity and S/G2/M cell cycle stage. Two of the clones tested, B12 and E2, reached sensitivity levels higher than those of UT7/Epo-S1 and CD36⁺ erythroid progenitor cells. These findings highlight the importance of cell cycle status for sensitivity to B19V, and we propose a promising new straightforward cell-based method for quantifying B19V infectious units. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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9 pages, 1113 KiB

Open AccessArticle

Changes in Mass Treatment of the Canine Parvovirus ICU Population in Relation to Public Policy Changes during the COVID-19 Pandemic

by Kevin Horecka, Nipuni Ratnayaka and Elizabeth A. Davis

Viruses 2020, 12(12), 1419; https://doi.org/10.3390/v12121419 - 10 Dec 2020

Cited by 1 | Viewed by 3065

Abstract

Previous work has indicated that canine parvovirus (CPV) prevalence in the Central Texas region may follow yearly, periodic patterns. The peak in CPV infection rates occurs during the summer months of May and June, marking a distinct “CPV season”. We hypothesized that human [...] Read more.

Previous work has indicated that canine parvovirus (CPV) prevalence in the Central Texas region may follow yearly, periodic patterns. The peak in CPV infection rates occurs during the summer months of May and June, marking a distinct “CPV season”. We hypothesized that human activity contributes to these seasonal changes in CPV infections. The COVID-19 pandemic resulted in drastic changes in human behavior which happened to synchronize with the CPV season in Central Texas, providing a unique opportunity with which to assess whether these society-level behavioral changes result in appreciable changes in CPV patient populations in the largest CPV treatment facility in Texas. In this work, we examine the population of CPV-infected patients at a large, dedicated CPV treatment clinic in Texas (having treated more than 5000 CPV-positive dogs in the last decade) and demonstrate that societal–behavioral changes due to COVID-19 were associated with a drastic reduction in CPV infections. This reduction occurred precisely when CPV season would typically begin, during the period immediately following state-wide “reopening” of business and facilities, resulting in a change in the typical CPV season when compared with previous years. These results provide evidence that changes in human activity may, in some way, contribute to changes in rates of CPV infection in the Central Texas region. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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15 pages, 11445 KiB

Open AccessArticle

Binding of CCCTC-Binding Factor (CTCF) to the Minute Virus of Mice Genome Is Important for Proper Processing of Viral P4-Generated Pre-mRNAs

by Maria Boftsi, Kinjal Majumder, Lisa R. Burger and David J. Pintel

Viruses 2020, 12(12), 1368; https://doi.org/10.3390/v12121368 - 30 Nov 2020

Cited by 5 | Viewed by 2153

Abstract

Specific chromatin immunoprecipitation of salt-fractionated infected cell extracts has demonstrated that the CCCTC-binding factor (CTCF), a highly conserved, 11-zinc-finger DNA-binding protein with known roles in cellular and viral genome organization and gene expression, specifically binds the genome of Minute Virus of Mice (MVM). [...] Read more.

Specific chromatin immunoprecipitation of salt-fractionated infected cell extracts has demonstrated that the CCCTC-binding factor (CTCF), a highly conserved, 11-zinc-finger DNA-binding protein with known roles in cellular and viral genome organization and gene expression, specifically binds the genome of Minute Virus of Mice (MVM). Mutations that diminish binding of CTCF to MVM affect processing of the P4-generated pre-mRNAs. These RNAs are spliced less efficiently to generate the R1 mRNA, and definition of the NS2-specific exon upstream of the small intron is reduced, leading to relatively less R2 and the generation of a novel exon-skipped product. These results suggest a model in which CTCF is required for proper engagement of the spliceosome at the MVM small intron and for the first steps of processing of the P4-generated pre-mRNA. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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15 pages, 2669 KiB

Open AccessArticle

Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis

by Tiago Ferreira, Amit Kulkarni, Clemens Bretscher, Karsten Richter, Marcelo Ehrlich and Antonio Marchini

Viruses 2020, 12(10), 1199; https://doi.org/10.3390/v12101199 - 21 Oct 2020

Cited by 9 | Viewed by 3768

Abstract

H-1 protoparvovirus (H-1PV) is a self-propagating virus that is non-pathogenic in humans and has oncolytic and oncosuppressive activities. H-1PV is the first member of the Parvoviridae family to undergo clinical testing as an anticancer agent. Results from clinical trials in patients with glioblastoma [...] Read more.

H-1 protoparvovirus (H-1PV) is a self-propagating virus that is non-pathogenic in humans and has oncolytic and oncosuppressive activities. H-1PV is the first member of the Parvoviridae family to undergo clinical testing as an anticancer agent. Results from clinical trials in patients with glioblastoma or pancreatic carcinoma show that virus treatment is safe, well-tolerated and associated with first signs of efficacy. Characterisation of the H-1PV life cycle may help to improve its efficacy and clinical outcome. In this study, we investigated the entry route of H-1PV in cervical carcinoma HeLa and glioma NCH125 cell lines. Using electron and confocal microscopy, we detected H-1PV particles within clathrin-coated pits and vesicles, providing evidence that the virus uses clathrin-mediated endocytosis for cell entry. In agreement with these results, we found that blocking clathrin-mediated endocytosis using specific inhibitors or small interfering RNA-mediated knockdown of its key regulator, AP2M1, markedly reduced H-1PV entry. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. We also show that H-1PV entry is dependent on dynamin, while viral trafficking occurs from early to late endosomes, with acidic pH necessary for a productive infection. This is the first study that characterises the cell entry pathways of oncolytic H-1PV. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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14 pages, 2451 KiB

Open AccessArticle

No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions

by Gloria Bua, Daniele Tedesco, Ilaria Conti, Alessandro Reggiani, Manuela Bartolini and Giorgio Gallinella

Viruses 2020, 12(9), 935; https://doi.org/10.3390/v12090935 - 25 Aug 2020

Cited by 5 | Viewed by 2927

Abstract

Parvovirus B19 (B19V), an ssDNA virus in the family Parvoviridae, is a human pathogenic virus, responsible for a wide range of clinical manifestations, still in need of effective and specific antivirals. DNA structures, including G-quadruplex (G4), have been recognised as relevant functional features [...] Read more.

Parvovirus B19 (B19V), an ssDNA virus in the family Parvoviridae, is a human pathogenic virus, responsible for a wide range of clinical manifestations, still in need of effective and specific antivirals. DNA structures, including G-quadruplex (G4), have been recognised as relevant functional features in viral genomes, and small-molecule ligands binding to these structures are promising antiviral compounds. Bioinformatic tools predict the presence of potential G4 forming sequences (PQSs) in the genome of B19V, raising interest as targets for antiviral strategies. Predictions locate PQSs in the genomic terminal regions, in proximity to replicative origins. The actual propensity of these PQSs to form G4 structures was investigated by circular dichroism spectroscopic analysis on synthetic oligonucleotides of corresponding sequences. No signature of G4 structures was detected, and the interaction with the G4 ligand BRACO-19 (N,N′-(9-{[4-(dimethylamino)phenyl]amino}acridine-3,6-diyl)bis(3-pyrrolidin-1-ylpropanamide) did not appear consistent with the stabilisation of G4 structures. Any potential role of PQSs in the viral lifecycle was then assessed in an in vitro infection model system, by evaluating any variation in replication or expression of B19V in the presence of the G4 ligands BRACO-19 and pyridostatin. Neither showed a significant inhibitory activity on B19V replication or expression. Experimental challenge did not support bioinformatic predictions. The terminal regions of B19V are characterised by relevant sequence and symmetry constraints, which are functional to viral replication. Our experiments suggest that these impose a stringent requirement prevailing over the propensity of forming actual G4 structures. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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13 pages, 3803 KiB

Open AccessArticle

Phylogenetic and Geospatial Evidence of Canine Parvovirus Transmission between Wild Dogs and Domestic Dogs at the Urban Fringe in Australia

by Mark Kelman, Lana Harriott, Maura Carrai, Emily Kwan, Michael P. Ward and Vanessa R. Barrs

Viruses 2020, 12(6), 663; https://doi.org/10.3390/v12060663 - 19 Jun 2020

Cited by 5 | Viewed by 3907

Abstract

Canine parvovirus (CPV) is an important cause of disease in domestic dogs. Sporadic cases and outbreaks occur across Australia and worldwide and are associated with high morbidity and mortality. Whether transmission of CPV occurs between owned dogs and populations of wild dogs, including [...] Read more.

Canine parvovirus (CPV) is an important cause of disease in domestic dogs. Sporadic cases and outbreaks occur across Australia and worldwide and are associated with high morbidity and mortality. Whether transmission of CPV occurs between owned dogs and populations of wild dogs, including Canis familiaris, Canis lupus dingo and hybrids, is not known. To investigate the role of wild dogs in CPV epidemiology in Australia, PCR was used to detect CPV DNA in tissue from wild dogs culled in the peri-urban regions of two Australian states, between August 2012 and May 2015. CPV DNA was detected in 4.7% (8/170). There was a strong geospatial association between wild-dog CPV infections and domestic-dog CPV cases reported to a national disease surveillance system between 2009 and 2015. Postcodes in which wild dogs tested positive for CPV were 8.63 times more likely to also have domestic-dog cases reported than postcodes in which wild dogs tested negative (p = 0.0332). Phylogenetic analysis of CPV VP2 sequences from wild dogs showed they were all CPV-2a variants characterized by a novel amino acid mutation (21-Ala) recently identified in CPV isolates from owned dogs in Australia with parvoviral enteritis. Wild-dog CPV VP2 sequences were compared to those from owned domestic dogs in Australia. For one domestic-dog case located approximately 10 km from a wild-dog capture location, and reported 3.5 years after the nearest wild dog was sampled, the virus was demonstrated to have a closely related common ancestor. This study provides phylogenetic and geospatial evidence of CPV transmission between wild and domestic dogs in Australia. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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15 pages, 1426 KiB

Open AccessCommunication

Phylogenetic, Evolutionary and Structural Analysis of Canine Parvovirus (CPV-2) Antigenic Variants Circulating in Colombia

by Sebastián Giraldo-Ramirez, Santiago Rendon-Marin and Julián Ruiz-Saenz

Viruses 2020, 12(5), 500; https://doi.org/10.3390/v12050500 - 30 Apr 2020

Cited by 26 | Viewed by 4479

Abstract

Canine parvovirus (CPV-2) is the causative agent of haemorrhagic gastroenteritis in canids. Three antigenic variants—CPV-2a, CPV-2b and CPV-2c—have been described, which are determined by variations at residue 426 of the VP2 capsid protein. In Colombia, the CPV-2a and CPV-2b antigenic variants have previously [...] Read more.

Canine parvovirus (CPV-2) is the causative agent of haemorrhagic gastroenteritis in canids. Three antigenic variants—CPV-2a, CPV-2b and CPV-2c—have been described, which are determined by variations at residue 426 of the VP2 capsid protein. In Colombia, the CPV-2a and CPV-2b antigenic variants have previously been reported through partial VP2 sequencing. Mutations at residues Asn428Asp and Ala514Ser of variant CPV-2a were detected, implying the appearance of a possible new CPV-2a variant in Colombia. The purpose of the present study was to characterise the full VP2 capsid protein in samples from Antioquia, Colombia. We conducted a cross-sectional study with 56 stool samples from dogs showing clinical symptoms of parvoviral disease. Following DNA extraction from the samples, VP2 amplification was performed using PCR and positive samples were sequenced. Sequence and phylogenetic analyses were performed by comparison with the VP2 gene sequences of the different CPV-2 worldwide. VP2 was amplified in 51.8% of the analysed samples. Sequencing and sequence alignment showed that 93.1% of the amplified samples belonged to the new CPV-2a antigenic variant previously. Analysing the amino acid sequences revealed that all CPV-2a contain Ala297Asn mutations, which are related to the South America I clade, and the Ala514Ser mutation, which allows characterization as a new CPV-2a sub-variant. The Colombian CPV-2b variant presented Phe267Tyr, Tyr324Ile and Thr440Ala, which are related to the Asia-I clade variants. The CPV-2c was not detected in the samples. In conclusion, two antigenic CPV-2 variants of two geographically distant origins are circulating in Colombia. It is crucial to continue characterising CPV-2 to elucidate the molecular dynamics of the virus and to detect new CPV-2 variants that could be becoming highly prevalent in the region. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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8 pages, 1572 KiB

Open AccessCommunication

Construction and Immunogenicity of Virus-Like Particles of Feline Parvovirus from the Tiger

by Cuicui Jiao, Hongliang Zhang, Wei Liu, Hongli Jin, Di Liu, Jian Zhao, Na Feng, Chuanmei Zhang and Jing Shi

Viruses 2020, 12(3), 315; https://doi.org/10.3390/v12030315 - 16 Mar 2020

Cited by 5 | Viewed by 3225

Abstract

Feline panleukopenia, caused by feline parvovirus (FPV), is a highly infectious disease characterized by leucopenia and hemorrhagic gastroenteritis that severely affects the health of large wild Felidae. In this study, tiger FPV virus-like particles (VLPs) were developed using the baculovirus expression system. The [...] Read more.

Feline panleukopenia, caused by feline parvovirus (FPV), is a highly infectious disease characterized by leucopenia and hemorrhagic gastroenteritis that severely affects the health of large wild Felidae. In this study, tiger FPV virus-like particles (VLPs) were developed using the baculovirus expression system. The VP2 gene from an infected Siberian tiger (Panthera tigris altaica) was used as the target gene. The key amino acids of this gene were the same as those of FPV, whereas the 101st amino acid was the same as that of canine parvovirus. Indirect immunofluorescence assay (IFA) results demonstrated that the VP2 protein was successfully expressed. SDS-PAGE and Western blotting (WB) results showed that the target protein band was present at approximately 65 kDa. Electron micrograph analyses indicated that the tiger FPV VLPs were successfully assembled and were morphologically similar to natural parvovirus particles. The hemagglutination (HA) titer of the tiger FPV VLPs was as high as 1:2¹⁸. The necropsy and tissue sections at the cat injection site suggested that the tiger FPV VLPs vaccine was safe. Antibody production was induced in cats after subcutaneous immunization, with a >1:2¹⁰ hemagglutination inhibition (HI) titer that persisted for at least 12 months. These results demonstrate that tiger FPV VLPs might provide a vaccine to prevent FPV-associated disease in the tiger. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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Review

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20 pages, 870 KiB

Open AccessReview

AMDV Vaccine: Challenges and Perspectives

by Nathan M. Markarian and Levon Abrahamyan

Viruses 2021, 13(9), 1833; https://doi.org/10.3390/v13091833 - 14 Sep 2021

Cited by 8 | Viewed by 3072

Abstract

Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control the viral spread have been limited to manual serological [...] Read more.

Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control the viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control the viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by the immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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16 pages, 2076 KiB

Open AccessReview

Concepts to Reveal Parvovirus–Nucleus Interactions

by Salla Mattola, Satu Hakanen, Sami Salminen, Vesa Aho, Elina Mäntylä, Teemu O. Ihalainen, Michael Kann and Maija Vihinen-Ranta

Viruses 2021, 13(7), 1306; https://doi.org/10.3390/v13071306 - 05 Jul 2021

Cited by 6 | Viewed by 5045

Abstract

Parvoviruses are small single-stranded (ss) DNA viruses, which replicate in the nucleoplasm and affect both the structure and function of the nucleus. The nuclear stage of the parvovirus life cycle starts at the nuclear entry of incoming capsids and culminates in the successful [...] Read more.

Parvoviruses are small single-stranded (ss) DNA viruses, which replicate in the nucleoplasm and affect both the structure and function of the nucleus. The nuclear stage of the parvovirus life cycle starts at the nuclear entry of incoming capsids and culminates in the successful passage of progeny capsids out of the nucleus. In this review, we will present past, current, and future microscopy and biochemical techniques and demonstrate their potential in revealing the dynamics and molecular interactions in the intranuclear processes of parvovirus infection. In particular, a number of advanced techniques will be presented for the detection of infection-induced changes, such as DNA modification and damage, as well as protein–chromatin interactions. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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21 pages, 3102 KiB

Open AccessReview

The VP1u of Human Parvovirus B19: A Multifunctional Capsid Protein with Biotechnological Applications

by Carlos Ros, Jan Bieri and Remo Leisi

Viruses 2020, 12(12), 1463; https://doi.org/10.3390/v12121463 - 18 Dec 2020

Cited by 9 | Viewed by 3758

Abstract

The viral protein 1 unique region (VP1u) of human parvovirus B19 (B19V) is a multifunctional capsid protein with essential roles in virus tropism, uptake, and subcellular trafficking. These functions reside on hidden protein domains, which become accessible upon interaction with cell membrane receptors. [...] Read more.

The viral protein 1 unique region (VP1u) of human parvovirus B19 (B19V) is a multifunctional capsid protein with essential roles in virus tropism, uptake, and subcellular trafficking. These functions reside on hidden protein domains, which become accessible upon interaction with cell membrane receptors. A receptor-binding domain (RBD) in VP1u is responsible for the specific targeting and uptake of the virus exclusively into cells of the erythroid lineage in the bone marrow. A phospholipase A₂ domain promotes the endosomal escape of the incoming virus. The VP1u is also the immunodominant region of the capsid as it is the target of neutralizing antibodies. For all these reasons, the VP1u has raised great interest in antiviral research and vaccinology. Besides the essential functions in B19V infection, the remarkable erythroid specificity of the VP1u makes it a unique erythroid cell surface biomarker. Moreover, the demonstrated capacity of the VP1u to deliver diverse cargo specifically to cells around the proerythroblast differentiation stage, including erythroleukemic cells, offers novel therapeutic opportunities for erythroid-specific drug delivery. In this review, we focus on the multifunctional role of the VP1u in B19V infection and explore its potential in diagnostics and erythroid-specific therapeutics. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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25 pages, 1403 KiB

Open AccessReview

Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches

by Olja Mijanović, Ana Branković, Anton V. Borovjagin, Denis V. Butnaru, Evgeny A. Bezrukov, Roman B. Sukhanov, Anastasia Shpichka, Peter Timashev and Ilya Ulasov

Viruses 2020, 12(4), 460; https://doi.org/10.3390/v12040460 - 18 Apr 2020

Cited by 10 | Viewed by 4619

Abstract

Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, effective delivery of a therapeutic gene into target [...] Read more.

Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, effective delivery of a therapeutic gene into target cells via AAV has been a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2020)

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