-
Journal of Virology Sep 2021Parvoviruses package a linear single-stranded DNA genome with hairpin structures at both ends. It has been thought that terminal hairpin sequences are indispensable for...
Parvoviruses package a linear single-stranded DNA genome with hairpin structures at both ends. It has been thought that terminal hairpin sequences are indispensable for viral DNA replication. Here, we provide evidence that the hairpin-deleted duplex genomes of human bocavirus 1 (HBoV1) replicate in human embryonic kidney 293 (HEK293) cells. We propose an alternative model for HBoV1 DNA replication in which the leading strand can initiate strand displacement without hairpin transfer. The transfection of the HBoV1 duplex genomes that retain a minimal replication origin at the right end () but with extensive deletions in the right-end hairpin (REH) generated viruses in HEK293 cells at a level 10 to 20 times lower than that of the wild-type (WT) duplex genome. Importantly, these viruses that have a genome with various deletions after the but not the one retaining only the replicated in polarized human airway epithelia. We discovered that the 18-nucleotide (nt) sequence (nt 5403 to 5420) beyond the was sufficient to confer virus replication in polarized human airway epithelia, although its progeny virus production was ∼5 times lower than that of the WT virus. Thus, our study demonstrates that hairpin transfer-independent productive parvovirus DNA replication can occur. Hairpin transfer-independent parvovirus replication was modeled with human bocavirus 1 (HBoV1) duplex genomes whose 5' hairpin structure was ablated by various deletions. In HEK293 cells, these duplex viral genomes with ablated 5' hairpin sequence replicated efficiently and generated viruses that productively infected polarized human airway epithelium. Thus, for the first time, we reveal a previously unknown phenomenon that productive parvovirus DNA replication does not depend on the hairpin sequence at REH to initiate rolling-hairpin DNA replication. Notably, the intermediates of viral DNA replication, as revealed by two-dimensional electrophoresis, from transfections of hairpin sequence-deleted duplex genome and full-length genome in HEK293 cells as well as from virus infection of polarized human airway epithelia are similar. Thus, the establishment of the hairpin transfer-independent parvoviral DNA replication deepens our understanding of viral DNA replication and may have implications in the development of parvovirus-based viral vectors with alternative properties.
Topics: DNA Replication; DNA, Viral; Epithelial Cells; Genome, Viral; HEK293 Cells; Human bocavirus; Humans; Inverted Repeat Sequences; Parvovirus; Replication Origin; Respiratory Mucosa; Viral Nonstructural Proteins; Virus Diseases; Virus Replication
PubMed: 34346761
DOI: 10.1128/JVI.01108-21 -
Virology Journal Oct 2021In line with the Latin expression "sed parva forti" meaning "small but mighty," the family Parvoviridae contains many of the smallest known viruses, some of which result... (Review)
Review
In line with the Latin expression "sed parva forti" meaning "small but mighty," the family Parvoviridae contains many of the smallest known viruses, some of which result in fatal or debilitating infections. In recent years, advances in metagenomic viral discovery techniques have dramatically increased the identification of novel parvoviruses in both diseased and healthy individuals. While some of these discoveries have solved etiologic mysteries of well-described diseases in animals, many of the newly discovered parvoviruses appear to cause mild or no disease, or disease associations remain to be established. With the increased use of animal parvoviruses as vectors for gene therapy and oncolytic treatments in humans, it becomes all the more important to understand the diversity, pathogenic potential, and evolution of this diverse family of viruses. In this review, we discuss parvoviruses infecting vertebrate animals, with a special focus on pathogens of veterinary significance and viruses discovered within the last four years.
Topics: Animals; Metagenomics; Parvoviridae; Parvoviridae Infections; Parvovirus; Phylogeny
PubMed: 34689822
DOI: 10.1186/s12985-021-01677-y -
Frontiers in Immunology 2019Cancer cells utilize multiple mechanisms to evade and suppress anticancer immune responses creating a "cold" immunosuppressive tumor microenvironment. Oncolytic... (Review)
Review
Cancer cells utilize multiple mechanisms to evade and suppress anticancer immune responses creating a "cold" immunosuppressive tumor microenvironment. Oncolytic virotherapy is emerging as a promising approach to revert tumor immunosuppression and enhance the efficacy of other forms of immunotherapy. Growing evidence indicates that oncolytic viruses (OVs) act in a multimodal fashion, inducing immunogenic cell death and thereby eliciting robust anticancer immune responses. In this review, we summarize information about OV-mediated immune conversion of the tumor microenvironment. As a case study we focus on the rodent protoparvovirus H-1PV and its dual role as an oncolytic and immune modulatory agent. Potential strategies to improve H-1PV anticancer efficacy are also discussed.
Topics: H-1 parvovirus; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 31440242
DOI: 10.3389/fimmu.2019.01848 -
Archives of Virology Sep 2022Viral enteritis is a significant threat to domestic dogs. The two primary pathogens that cause viral enteritis in dogs are canine coronavirus (CCoV) and canine...
Viral enteritis is a significant threat to domestic dogs. The two primary pathogens that cause viral enteritis in dogs are canine coronavirus (CCoV) and canine parvovirus (CPV). In this study, we investigated the occurrence of CPV-2, CCoV, and canine circovirus coinfection by characterizing circulating subtypes of CPV-2 in faecal samples from symptomatic dogs admitted to veterinary clinics located in Ankara, Elazığ, Kayseri, and Kocaeli provinces of Turkey, between 2019 and 2022. Virus detection by PCR and RT-PCR revealed that CPV-2 was present in 48 (77.4%) samples, and no other agents were detected. Based on the occurrence of the codon GAT at positions 1276 to 1278 (coding for aspartate at residue 426) of VP2, all CPV-2 isolates were confirmed to be of the CPV-2b subtype. The complete genome sequences of two CPV-2b isolates showed a high degree of similarity to and phylogenetic clustering with Australian and East Asian strains/isolates. The predominant CPV strain circulating in the three different regions of Turkey was found to be a CPV-2b strain containing the amino acid substitutions at Y324I and T440A, which commonly contribute to immune escape. This is the first report of complete genomic analysis of CPV-2 isolates circulating in symptomatic domestic dogs in Turkey. The evolution of CPV-2 has raised questions about the efficacy of current vaccination regimes and highlights the importance of monitoring the emergence and spread of new CPV-2 variants.
Topics: Animals; Australia; Coronavirus, Canine; Dog Diseases; Dogs; Enteritis; Genomics; Parvoviridae Infections; Parvovirus, Canine; Phylogeny; Turkey
PubMed: 35716267
DOI: 10.1007/s00705-022-05509-4 -
Preventive Veterinary Medicine Jan 2020Infection of canids with canine parvovirus (CPV) can result in severe, often fatal disease. This study aimed to examine climatic, socioeconomic and geographic risk...
Infection of canids with canine parvovirus (CPV) can result in severe, often fatal disease. This study aimed to examine climatic, socioeconomic and geographic risk factors for CPV infection and CPV-associated euthanasia in Australia. Australian veterinary hospital responses (534; 23.5 %) to a national veterinary survey of CPV case occurrences and euthanasias in 2016 were used. Severe caseloads (>40 cases per annum) were reported by 26 (11 %) hospitals (median 60 cases; IQR 50-110). Case reporting, case numbers, and without-treatment euthanasia were significantly associated with disadvantage across all Socio-Economic Index for Areas quintiles (p < 0.0001) - the greater the disadvantage, the more reports. Strong negative correlations were found between case numbers and the Index of Relative Socioeconomic Disadvantage (r = -0.3357, p < 0.0001) and also between euthanasia and the Index of Education and Occupation (r = -0.3762, p < 0.0001). Hospitals in more remote areas were also more likely to report cases and to euthanize without treatment (p < 0.0001). Of the climate variables, temperature of the hottest month was most strongly positively correlated with case numbers (r = 0.421, p < 0.0001), and lower annual rainfall was associated with more case-reporting hospitals (p < 0.0001). These results confirm that socioeconomic disadvantage is a significant risk-factor for CPV infection and outcome, and high temperature may also contribute to risk.
Topics: Animals; Australia; Climate; Dog Diseases; Dogs; Euthanasia, Animal; Geography; Parvoviridae Infections; Parvovirus, Canine; Risk Factors; Socioeconomic Factors
PubMed: 31739219
DOI: 10.1016/j.prevetmed.2019.104816 -
BMC Veterinary Research Apr 2022Classical porcine parvovirus (PPV1) and novel porcine parvoviruses designated porcine parvovirus 2 through 7 (PPV2-PPV7) are widespread in pig populations. The objective...
BACKGROUND
Classical porcine parvovirus (PPV1) and novel porcine parvoviruses designated porcine parvovirus 2 through 7 (PPV2-PPV7) are widespread in pig populations. The objective of this study was to investigate the prevalence rates of PPV1-PPV7 in Korea by detecting PPVs in serum, lung and fecal samples and to elucidate the association of PPVs with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory virus (PRRSV), major pathogens involved in porcine respiratory disease complex (PRDC). A total of 286 serum, 481 lung, and 281 fecal samples collected from 2018 to 2020 were analyzed.
RESULTS
The results showed that PPVs are widespread in Korea; the highest detection rates were found in lung samples and ranged from 7.9% (PPV1) to 32.6% (PPV2). Regarding age groups, fattening pigs had the highest detection rates of PPVs, ranging from 6.4% (PPV1) to 36.5% (PPV6); this finding suggests the chronic nature of PPV infections and the continual circulation of these viruses. When compared with PCV2- and PRRSV-negative lung samples, PCV2-positive samples with or without PRRSV positivity had significantly higher detection levels of PPV1 and PPV6. In contrast, the prevalence of PPV2 and PPV7 was significantly higher in PRRSV-infected lung samples regardless of PCV2 detection. PPV5 was detected significantly more frequently in samples with both PCV2 and PRRSV positivity.
CONCLUSIONS
This study could offer a better understanding of the role of PPVs in PCV2 and/or PRRSV infection though further studies are needed to experimentally assess the impact of PPVs in coinfections.
Topics: Animals; Circoviridae Infections; Circovirus; Parvoviridae Infections; Parvovirus, Porcine; Porcine Reproductive and Respiratory Syndrome; Porcine respiratory and reproductive syndrome virus; Prevalence; Swine; Swine Diseases
PubMed: 35395853
DOI: 10.1186/s12917-022-03236-1 -
BMC Veterinary Research Jun 2020Sepsis is a severe condition associated with high prevalence and mortality rates. Parvovirus enteritis is a predisposing factor for sepsis, as it promotes intestinal...
BACKGROUND
Sepsis is a severe condition associated with high prevalence and mortality rates. Parvovirus enteritis is a predisposing factor for sepsis, as it promotes intestinal bacterial translocation and severe immunosuppression. This makes dogs infected by parvovirus a suitable study population as far as sepsis is concerned. The main objective of the present study was to evaluate the differences between two sets of SIRS (Systemic Inflammatory Response Syndrome) criteria in outcome prediction: SIRS 1991 and SIRS 2001. The possibility of stratifying and classifying septic dogs was assessed using a proposed animal adapted PIRO (Predisposition, Infection, Response and Organ dysfunction) scoring system.
RESULTS
The 72 dogs enrolled in this study were scored for each of the PIRO elements, except for Infection, as all were considered to have the same infection score, and subjected to two sets of SIRS criteria, in order to measure their correlation with the outcome. Concerning SIRS criteria, it was found that the proposed alterations on SIRS 2001 (capillary refill time or mucous membrane colour alteration) were significantly associated with the outcome (OR = 4.09, p < 0.05), contrasting with the 1991 SIRS criteria (p = 0.352) that did not correlate with the outcome. No significant statistical association was found between Predisposition (p = 1), Response (p = 0.1135), Organ dysfunction (p = 0.1135), total PIRO score (p = 0.093) and outcome. To explore the possibility of using the SIRS criteria as a fast decision-making tool, a Fast-and-Frugal tree (FFT) was created with a sensitivity of 92% and a specificity of 29%.
CONCLUSION
These results suggest that increasing the SIRS criteria specificity may improve their prognostic value and their clinical usefulness. In order to improve the proposed PIRO scoring system outcome prediction ability, more specific criteria should be added, mainly inflammatory and organ dysfunction biomarkers.
Topics: Animals; Dog Diseases; Dogs; Enteritis; Female; Male; Parvoviridae Infections; Parvovirus, Canine; Prognosis; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome
PubMed: 32539830
DOI: 10.1186/s12917-020-02417-0 -
Viruses Sep 2019Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have... (Review)
Review
Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens.
Topics: Animal Diseases; Animals; Cats; Diarrhea; Enterovirus Infections; Gastroenteritis; Kobuvirus; Norovirus; Parvovirus; Phylogeny; Viruses
PubMed: 31575055
DOI: 10.3390/v11100908 -
Virology Journal Feb 2018Goose parvovirus (GPV) causes acute enteritis, hepatitis, myocarditis and high morbidity and mortality in geese and ducks. GPV H strain was isolated from a Heilongjiang...
BACKGROUND
Goose parvovirus (GPV) causes acute enteritis, hepatitis, myocarditis and high morbidity and mortality in geese and ducks. GPV H strain was isolated from a Heilongjiang goose farm where the geese were showing signs of hemorrhage in the brain, liver, and intestinal tract. In this study, we explored the genetic diversity among waterfowl parvovirus isolates and the pathological characteristics of GPV H in Shaoxing ducklings.
METHODS
The complete capsid protein (VP) and non-structural (NS) sequences of the isolated H strain were sequenced, and phylogenetic trees of VP and NS were constructed in MEGA version 5.05 using the neighbor-joining method. Three-day-old Shaoxing ducklings were inoculated with GPV and were euthanized at 1, 2, 4, 6, and 8 days post-inoculation (PI), and their organs were removed and collected. The organs of 6-day PI ducklings were fixed in formalin, embedded in paraffin, sectioned for histology, stained with HE and analyzed for pathological lesions. The distribution of the GPV H strain in the tissues of the inoculated ducklings was detected using the polymerase chain reaction (PCR) method.
RESULTS
Genetic analysis of the NS and VP genes indicated that the H strain was closely related to strains circulating in China during 1999-2014, and the nucleic acid identity of those strains was 98%-99%. Classical symptoms were observed in the inoculated ducklings. GPV remained in many tissues and replicated in a majority of the tissues, leading to histopathological lesions in four tissues.
CONCLUSIONS
We first reported the distribution and histopathological lesions of a Chinese strain of GPV in infected shaoxing ducklings. This H strain was moderate pathogenic for Shaoxing ducklings.
Topics: Animals; Biopsy; Cell Line; China; Ducks; Geese; Genes, Viral; Genome, Viral; Parvoviridae Infections; Parvovirus; Phylogeny; Poultry Diseases; Sequence Analysis, DNA
PubMed: 29391035
DOI: 10.1186/s12985-018-0935-5 -
Viruses Jan 2022Porcine parvovirus (PPV) is the main pathogen of reproductive disorders. In recent years, a new type of porcine parvovirus has been discovered and named porcine...
Porcine parvovirus (PPV) is the main pathogen of reproductive disorders. In recent years, a new type of porcine parvovirus has been discovered and named porcine parvovirus 2 to 7 (PPV2-PPV7), and it is associated with porcine circovirus type 2 in pigs. Codon usage patterns and their effects on the evolution and host adaptation of different PPV sub-types are still largely unknown. Here, we define six main sub-types based on the Bayesian method of structural proteins of each sub-type of PPV, including PPV2, PPV3, PPV4, PPV5, PPV6, and PPV7, which show different degrees of codon usage preferences. The effective number of codons (ENC) indicates that all PPV sub-types have low codon bias. According to the codon adaptation index (CAI), PPV3 and PPV7 have the highest similarity with the host, which is related to the main popular tendency of the host in the field; according to the frequency of optimal codons (FOP), PPV7 has the highest frequency of optimal codons, indicating the most frequently used codons in its genes; and according to the relative codon deoptimization index (RCDI), PPV3 has a higher degree. Therefore, it is determined that mutational stress has a certain impact on the codon usage preference of PPV genes, and natural selection plays a very decisive and dominant role in the codon usage pattern. Our research provides a new perspective on the evolution of porcine parvovirus (PPV) and may help provide a new method for future research on the origin, evolutionary model, and host adaptation of PPV.
Topics: Animals; Bayes Theorem; Codon Usage; Evolution, Molecular; Genetic Variation; Genotype; Host Adaptation; Mutation; Parvoviridae Infections; Parvovirus, Porcine; Phylogeny; Selection, Genetic; Swine; Swine Diseases
PubMed: 35215764
DOI: 10.3390/v14020170