1,721,204 research outputs found
SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
Full text linkA new pandemic caused by the betacoronavirus SARS-CoV-2 originated in China in late 2019. Although often asymptomatic, a relevant percentage of affected people can develop severe pneumonia. Initial evidence suggests that dysregulation of the immune response could contribute to the pathogenesis, as previously demonstrated for SARS-CoV. The presence of genome composition features involved in delaying viral recognition is herein investigated for human coronaviruses (HCoVs), with a special emphasis on SARS-CoV-2. A broad collection of HCoVs polyprotein, envelope, matrix, nucleocapsid and spike coding sequences was downloaded and several statistics representative of genome composition and codon bias were investigated. A model able to evaluate and test the presence of a significant under- or over-representation of dinucleotide pairs while accounting for the underlying codon bias and protein sequence was also implemented. The study revealed the significant under-representation of CpG dinucleotide pair in all HcoV, but especially in SARS-CoV and even more in SARS-CoV-2. The presence of forces acting to minimize CpG content was confirmed by relative synonymous codon usage pattern. Codons containing the CpG pair were severely under-represented, primarily in the polyprotein and spike coding sequences of SARS-CoV-2. Additionally, a significant under-representation of the TpA pair was observed in the N and S region of SARS-CoV and SARS-CoV-2. Increasing experimental evidence has proven that CpG and TpA are targeted by innate antiviral host defences, contributing both to RNA degradation and RIG-1 mediated interferon production. The low content of these dinucleotides could contribute to a delayed interferon production, dysregulated immune response, higher viral replication and poor outcome. Significantly, the RIG-1 signalling pathway was proven to be defective in elderlies, suggesting a likely interaction between limited viral recognition and lower responsiveness in interferon production that could justify the higher disease severity and mortality in older patients
Further insight into the molecular epidemiology and evolutionary dynamics of rapidly evolving RNA and ssDNA viruses
Full text linkRapidly evolving RNA and ssDNA viruses represent a fascinating field characterized by a strict interconnection between the “speculative” study of viral evolution and its practical implications in everyday veterinary medicine.
This thesis has been thought as a collection of manuscripts that aimed to investigate different aspects and levels of viral evolution while still maintaining a focus on practical repercussions. Even if different infectious diseases and etiological agents are considered, they are all functional to the study of different aspects and implications of rapid virus evolution.
Considering the heterogeneous nature of the manuscripts, they have been organized according to a “crescent” scale, starting from the lowest scale of viral evolution and progressing to broader scales.
The manuscript “Viral subpopulations in aMPV vaccines are unlikely to be responsible for reversion to virulence.” addresses a fine-level analysis of the population structure of the AMPV subtype B live attenuated vaccine and its potential role in the previously demonstrated phenomenon of reversion to virulence.
The widespread administration of live attenuated vaccines, despite their obvious advantages in terms of reducing disease prevalence, clinical signs and economic losses, is associated with costs that are not limited to the risk of reversion to virulence or to direct economic costs. Based on a wide collection of Italian samples, “Continued use of IBV 793B vaccine needs reassessment after its withdrawal led to the genotype’s disappearance” reports the impact of these vaccines in complicating the diagnostic process and, as a consequence, the interpretation of the epidemiological scenario in the absence of known vaccine markers.
Obviously, updated knowledge of the strains currently circulating in a particular area is of great relevance for the implementation of proper control strategies. With this aim in mind, a field survey, which is published in “Field survey of Avian Metapneumovirus in Northern Italy”, was conducted on hundreds of Italian farms to estimate and characterize the AMPV strains circulating in our country. To further support frequent and extensive surveys, an assay that is able to detect, quantify and genotype the two AMPV subtypes currently circulating in Italy was developed and validated. Because economic constraints often represent a major limit, efforts were made to reduce the assay costs compared with other real-time RT-PCR methods while still guaranteeing comparable or superior performances (“A Sensitive, Reproducible, and Economic Real-Time Reverse Transcription PCR Detecting Avian Metapneumovirus Subtypes A and B”).
Unfortunately, the diagnosis of rapidly evolving RNA viruses is itself an arduous task that requires a continuous evaluation and updating of diagnostic tools, even in laboratory that receive samples from limited geographic areas. The manuscripts entitled “Observation of high recombination occurrence of Porcine reproductive and respiratory syndrome virus in field condition” and “Phylodynamic analysis of Porcine reproductive and respiratory syndrome virus (PRRSV) in Italy: action of selective pressures and interactions between different clades.” address the study of the molecular epidemiology of Porcine reproductive and respiratory syndrome virus (PRRSV) in Italy considering the evolutionary forces driving PRRSV evolution at the local scale (i.e., high substitution rate, recombination, interaction between different clades and action of selective pressures). The high heterogeneity of PRRSV in the national contest was then evaluated with respect to the challenges that it poses in the development and validation of RT-PCR- and qRT-PCR-based diagnostic methods (“Validation and comparison of different end point and real time RT-PCR assays for detection and genotyping of porcine reproductive and respiratory syndrome virus”) and assessing its impact on diagnostic accuracy (“The impact of porcine reproductive and respiratory syndrome virus genetic heterogeneity on molecular assay performances”). Similarly, “International trades, local spread and viral evolution: the case of Porcine circovirus type 2 (PCV2) strains heterogeneity in Italy” investigates the genetic variability of PCV2 within national borders and compares it with the knowledge of its molecular epidemiology available from other countries. This study provides evidence regarding the role of both “in loco” evolution and importation of different genotypes and strains from foreign countries in determining the Italian PCV2 genetic heterogeneity. The crescent amount of PCV2 sequences deposited in publically available databases has revealed its marked variability and challenged the current classification criteria. Nevertheless, at least a superficial knowledge of the PCV2 molecular epidemiology is mandatory for the planning and evaluation of control strategies. “Revisiting the Taxonomical classification of PCV2: still a real challenge” proposes new criteria for the classification of PCV2 into different genotypes. Our aim was to provide a scheme that both accounts for the constraint imposed by the biological proprieties of this virus and allows a rapid, practical and easy way to classify PCV2 strains even during routine diagnostic activity. Last, “Genetic characterisation of porcine circovirus type 2 (PCV2) strains from feral pigs in the Brazilian Pantanal: an opportunity to reconstruct the history of PCV2 evolution” investigates more speculative issues inherent to the PCV2 origin. The discovery of a PCV2c genotype, which, to date, was believed to be extinct, in a feral pig population characterized by a peculiar population history and by a complex, and still partially known, relationship network with other PCV2-susceptible species opens exciting scenarios concerning the history and origin of PCV
Six underreported viral diseases of domesticated and wild swine in Africa: Implications and perspectives
No full text: Pig production is increasing annually in Africa as it is recognized as a significant source of income, livelihood and food security, particularly in rural communities. Understanding the circulating swine pathogens is crucial for the success of this emerging industry. Although there is extensive data available on the African swine fever virus due to its devastating impact on pig production, knowledge about the presence of other viral swine pathogens on the continent is still extremely limited. This review discusses what is currently known about six swine pathogens in Africa: classical swine fever virus, porcine reproductive and respiratory syndrome virus, porcine circovirus-2, porcine circovirus-3, porcine parvovirus-1, and pseudorabies virus. Gaps in our knowledge are identified and topics of future focus discussed
Porcine circovirus 3 (PCV-3) variability : Is it in the virus or in the classification criteria?
Full text linkThe continuous discovery of new viruses during the last decades has increased the need for new classification approaches and rules. Currently, the International Committee on Taxonomy of Viruses classifies viruses up to the species level. However, because of the higher variability of most of these infectious agents, a below-species categorization is often required for proper epidemiological investigations. Unfortunately, variable criteria are typically proposed by different research groups, leading to misleading and poorly reproducible results. This scenario occurred for the recently identified Porcine circovirus 3. Although genotype definition standards had been defined by a group of experts in the field, recent articles have been published introducing new genotypes, whose classification rules are not reported. We therefore would like to stress the usefulness of defining and maintaining a common language to allow proper results comparison among groups. We consider the consensus opinion of a heterogeneous expert team as the most valuable approach. Nevertheless, if other approaches are proposed, the disclosure of the criteria and the comparison with previous literature should be deemed mandatory to allow effective results reproducibility, interpretation and sharing
STUDIO DEL FENOMENO DELLA RICOMBINAZIONE TRA STIPITI DI PRRSV CIRCOLANTI IN ALLEVAMENTI DEL NORD ITALIA
No full textLa ricombinazione tra differenti stipiti del virus della PRRSV è stata riportata sia in vitro sia in
vivo. Ciononostante evidenze di ricombinazione da studi di campo sono rare e principalmente
ottenute dalla comparazione di sequenze da campionamenti su larga scala. Questo studio è
rivolto ad indagare questo fenomeno su piccola scala usando 162 campioni ottenuti da suini
di allevamenti di tre regioni del Nord Italia e raccolti tra il 2009 e il 2012.
L’analisi di ricombinazione è stata condotta su ORF5, ORF7 e loro concatenazione tramite il
programma RDP3. È stata eseguita la predizione in silico degli epitopi target della GP5 degli
stipiti ricombinanti più signiicativi. La storia ilogeograica dei pattern di migrazione degli
stipiti di PRRSV, considerando la provincia come livello minimo, è stata ricostruita usando
l’approccio bayesiano implementato in BEAST. In totale sono state ottenute le sequenze di
114 ORF5, 84 ORF7 e 50 sequenze concatenate. È stata evidente la predizione di tre eventi
di ricombinazione. Due mostravano almeno un breakpoint nella regione non sequenziata
tra ORF5 e ORF7, il terzo evento comprendeva la regione di ORF5 includendo parte del
maggiore epitopo di neutralizzazione. L’identiicazione a distanza di tempo degli stessi
stipiti ricombinanti nella medesima azienda depone a favore di una loro signiicativa itness.
L’analisi ilogeograica ha rivelato alcuni tassi di migrazione adeguatamente supportati da
signiicatività statistica
Impatto di differenti strategie vaccinali sulle dinamiche di popolazione del genotipo QX di Bronchite infettiva e sulla frequenza dei focolai
No full textL’estrema variabilità e la rapida evoluzione del virus della bronchite infettiva (IBV) hanno sempre rappresentato la sfida principale per il suo controllo a causa della limitata cross-protezione fra i diversi ceppi. Vari studi sperimentali hanno dimostrato un incremento nello spettro di protezione qualora gli animali siano vaccinati con più genotipi differenti. Ciò non di meno, le condizioni e la tempistica di somministrazione della vaccinazione in campo sono a tal punto differenti che spesso una generalizzazione dei risultati sperimentali è quantomeno questionabile. Nel presente studio è stato utilizzato un approccio di tipo epidemiologico-filodinamico per ricostruire la storia demografica del principale genotipo di campo (i.e. genotipo QX) circolante in Italia. Centonovantacinque campioni raccolti nel periodo 2012-2016 sono stati sequenziati e analizzati. Ciò ha permesso di evidenziare come sia le dinamiche di popolazione di questo virus che la frequenza di focolai clinici siano state particolarmente variabili nel corso del tempo. Di particolare rilievo è risultata la forte associazione fra questi fenomeni e i cambiamenti nelle strategie vaccinali adottate. Ciò ha permesso di dimostrare il rapporto di causa-effetto fra la somministrazione/sospensione del vaccino per IBV e le ripercussioni in termini di dimensione della popolazione virale e, soprattutto, dell’occorrenza di episodi clinici indotti da IBV. È stato quindi possibile fornire una robusta dimostrazione dell’effetto protettivo indotto della vaccinazione nella pratica routinaria di allevamento. Inoltre, il resoconto qui riportato evidenzia l’importanza di pianificare con rigore non solo le strategie di controllo ma anche il loro monitoraggio e la loro valutazione, evitando di affidarsi a pareri soggettivi ed estemporanei
Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study
Full text linkSince their commercialization, vaccines against Porcine circovirus type 2 (PCV2) have been the cornerstone control strategy. Nevertheless, the periodic emergence of new genotype waves and the recent reports of vaccine failure outbreaks have raised the question if widespread vaccination strategies could have driven viral evolution and affected different genotype fitness. To investigate this issue an in-deep analysis, based on a bioinformatics and biostatistics approach, has been implemented. ORF2 sequences from vaccinated and non-vaccinated populations (i.e. domestic pigs before and after vaccine introduction and wild boars) were considered. The action of selective forces on PCV2 strains has been analyzed and compared among groups. Remarkable differences were found in the selective forces acting on viral populations circulating in different “immune environments”. Particularly for PCV2a, a directional selection promoting a change in the viral capsid away from the vaccine specific antigenic determinants has been detected after vaccine introduction. Involved amino acids were previously reported to be part of viral epitopes whose variability is responsible of immune escape. Our findings support a change in PCV2 evolutionary pattern after widespread vaccination introduction and stress once more the compulsoriness of a continuous monitoring of PCV2 epidemiology to promptly act in response to the emergence of possible vaccine-escaping mutants
Evidence of PRRSV recombination from field samples in northeastern Italy
No full textRecombination of different PRRSV strains has been reported both in vitro and in vivo. However field evidences of recombination are rare and mainly obtained comparing sequences from large-scale sampling (i.e. countries). This work investigates this phenomenon on a smaller scale using 213 samples (serum and lung) originating from three regions of northeastern Italy, collected during 2009-2012. The presence of rapid and effective transmission of moderately different strains between farms creates appropriate conditions for co-infection to occur, justifying the high number of recombination events recorded. Further studies and field sampling should be devoted to demonstrate the effect of recombination on viral fitness and pathogenicity, providing further insight in the still highly debated role of recombination on PRRSV evolution
A comprehensive view of the infectious bursal disease virus epidemiological landscape in Africa
Full text linkPhylodynamic analysis of porcine circovirus type 2 reveals global waves of emerging genotypes and the circulation of recombinant forms
Full text linkSince the first description of Porcine circovirus type 2 (PCV2), four genotypes (PCV2a, PCV2b, PCV2c and PCV2d) have been recognized and three of them have been shown to exhibit worldwide distribution. Here, the population dynamics of PCV2 has been reconstructed over time and the factors that have shaped its evolution determined. The results obtained confirm that PCV2 originated approximately at the beginning of the 20th century. The most recent common ancestor of genotypes PCV2a, PCV2b, PCV2c and PCV2d circulated in the 1950s, 1980s, 1960s and 1950s, respectively, and the population sizes of the individual genotypes remained low until the mid 90s, coinciding with the identification of PCV2 as a major pathogen of the pig industry.
The population dynamics of PCV2 have been characterized by the appearance of periodic waves of distinct genotypes that, after an initial rise, spread following major swine commercial routes and were then superseded by subsequent emerging genotypes. Various recombinant forms displayed comparable population dynamics and spreading routes to those of major genotypes, suggesting that recombinant strains are able to compete with parental ones. The capsid gene is subjected to immune selection and evasion of the host immune response seems to be a major force for the emergence and spread of new genotypes. In contrast, the evolution of other genes appears to be constrained by the particular genomic organization of PCV2. In summary, obtained results suggest that changes in farming strategies, international trade, host population immunity, recombination and the constraints imposed by genome organization have all played a major role in the evolutionary dynamics of PCV2
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