Academic literature on the topic 'Orthoparamyxovirinae'

The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a mini-replicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to.

Measles is a highly transmissible respiratory infection due to an enveloped, negative single-stranded RNA virus, belonging to the genus Morbillivirus, the family Paramyxoviridae and the subfamily Orthoparamyxovirinae [...]

Chiroptera are one of the most diverse mammal orders. They are considered reservoirs of main human pathogens, where coronaviruses (CoVs) and paramyxoviruses (PMVs) may be highlighted. Moreover, the growing number of publications on CoVs and PMVs in wildlife reinforces the scientific community’s interest in eco-vigilance, especially because of the emergence of important human pathogens such as the SARS-CoV-2 and Nipha viruses. Considering that Brazil presents continental dimensions, is biologically rich containing one of the most diverse continental biotas and presents a rich biodiversity of animals classified in the order Chiroptera, the mapping of CoV and PMV genetics related to human pathogens is important and the aim of the present work. CoVs can be classified into four genera: Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus. Delta- and gammacoronaviruses infect mainly birds, while alpha- and betacoronaviruses contain important animal and human pathogens. Almost 60% of alpha- and betacoronaviruses are related to bats, which are considered natural hosts of these viral genera members. The studies on CoV presence in bats from Brazil have mainly assayed phyllostomid, molossid and vespertilionid bats in the South, Southeast and North territories. Despite Brazil not hosting rhinophilid or pteropodid bats, which are natural reservoirs of SARS-related CoVs and henipaviruses, respectively, CoVs and PMVs reported in Brazilian bats are genetically closely related to some human pathogens. Most works performed with Brazilian bats reported alpha-CoVs that were closely related to other bat-CoVs, despite a few reports of beta-CoVs grouped in the Merbecovirus and Embecovirus subgenera. The family Paramyxoviridae includes four subfamilies (Avulavirinae, Metaparamyxovirinae, Orthoparamyxovirinae and Rubulavirinae), and bats are significant drivers of PMV cross-species viral transmission. Additionally, the studies that have evaluated PMV presence in Brazilian bats have mainly found sequences classified in the Jeilongvirus and Morbillivirus genera that belong to the Orthoparamyxovirinae subfamily. Despite the increasing amount of research on Brazilian bats, studies analyzing these samples are still scarce. When surveying the representativeness of the CoVs and PMVs found and the available genomic sequences, it can be perceived that there may be gaps in the knowledge. The continuous monitoring of viral sequences that are closely related to human pathogens may be helpful in mapping and predicting future hotspots in the emergence of zoonotic agents.

Bats are known as typical reservoirs for a number of viruses, including viruses of the family Paramyxoviridae. Representatives of the subfamily Orthoparamyxovirinae are distributed worldwide and can cause mild to fatal diseases when infecting humans. The research on Paramyxoviruses (PMVs) from different bat hosts all over the world aims to understand the diversity, evolution and distribution of these viruses and to assess their zoonotic potential. A high number of yet unclassified PMVs from bats are recorded. In our study, we investigated bat species from the families Rhinolophidae, Hipposiderae, Pteropodidae and Miniopteridae that are roosting sympatrically in the Wavul Galge cave (Koslanda, Sri Lanka). The sampling at three time points (March and July 2018; January 2019) and screening for PMVs with a generic PCR show the presence of different novel PMVs in 10 urine samples collected from Miniopterus fuliginosus. Sequence analysis revealed a high similarity of the novel strains among each other and to other unclassified PMVs collected from Miniopterus bats. In this study, we present the first detection of PMVs in Sri Lanka and the presence of PMVs in the bat species M. fuliginosus for the first time.

Wild species are susceptible to several typical domestic animal pathogens, and the increasingly close contact between these groups is a predictive factor for disease exposure. Some viruses are important and old-known, and others are emerging or reemerging for domestic carnivorans and have been identified as threats to the conservation of wild mammals. The purpose of the study was to investigate the occurrence of bocaparvoviruses (BoVs, Parvoviridae family, Parvovirinae subfamily, Bocaparvovirus genus), parvoviruses (Parvoviridae family, Parvovirinae subfamily, Protoparvovirus genus, Protoparvovirus carnivoran1), hepadnaviruses (Hepadnaviridae family), coronaviruses (Coronaviridae family, Orthocoronavirinae subfamily), paramyxoviruses (Paramyxoviridae family) and canine distemper virus (Orthoparamyxovirinae subfamily, Morbillivirus genus, Morbillivirus canis), poxviruses (Poxviridae family), feline herpesvirus (Orthoherpesviridae family, Alphaherpesvirinae subfamily, Varicellovirus genus, Varicellovirus felidalpha1), feline calicivirus (Caliciviridae family, Vesivirus genus, FCV), feline immunodeficiency virus (Retroviridae family, Orthoretrovirinae subfamily, Lentivirus genus, FIV), feline leukemia virus (Retroviridae family, Orthoretrovirinae subfamily, Gammaretrovirus genus, FeLV), and gammaherpesviruses (Orthoherpesviridae family, Gammaherpesvirinae subfamily) in wild carnivorans. A total of 30 biological samples from the families Canidae, Felidae, Mephitidae, Mustelidae, and Procyonidae were evaluated. All animals were victims of vehicular collisions in the state of Mato Grosso do Sul, Brazil. Canine parvovirus (CPV-2) DNA was detected in the spleen of a bush dog (Speothos venaticus), a jaguarundi (Puma yagouaroundi), and a jaguar (Panthera onca), FeLV proviral DNA was found in the spleen of an ocelot (Leopardus pardalis); while CDV RNA was detected in the liver of a jaguarundi. Phylogenetic analysis carried out with the partial sequence of the CPV-2 VP2 gene and the U3 (LTR) gag region of FeLV showed 100% identity with strains obtained from domestic dogs and cats, respectively. The approximation between wild and domestic animals favors the transmission of pathogens, especially between phylogenetically close species, such as members of the Canidae and Felidae families. Identification of the DNA and RNA of potentially fatal viruses such as CPV-2, FeLV, and CDV in four wilds endangered to extinction and understudied species contributes to our understanding of the pathogens circulating in this free-ranging and vulnerable population.

Abstract The subfamily Orthoparamyxovirinae is a group of single-stranded, negative-sense RNA viruses that contains many human, animal and zoonotic pathogens. While there are currently only 42 recognized species in this subfamily, recent research has revealed that much of its diversity remains to be characterized. Using a newly developed nested PCR-based screening assay, we report here the discovery of fifteen orthoparamyxoviruses in rodents and shrews from Belgium and Guinea, thirteen of which are believed to represent new species. Using a combination of nanopore and sanger sequencing, complete genomes could be determined for almost all these viruses, enabling a detailed evaluation of their genome characteristics. While most viruses are thought to belong to the rapidly expanding genus Jeilongvirus, we also identify novel members of the genera Narmovirus, Henipavirus and Morbillivirus. Together with other recently discovered orthoparamyxoviruses, both henipaviruses and the morbillivirus discovered here appear to form distinct rodent-/shrew-borne clades within their respective genera, clustering separately from all currently classified viruses. In the case of the henipaviruses, a comparison of the different members of this clade revealed the presence of a secondary conserved open reading frame, encoding for a transmembrane protein, within the F gene, the biological relevance of which remains to be established. While the characteristics of the viruses described here shed further light on the complex evolutionary origin of paramyxoviruses, they also illustrate that the diversity of this group of viruses in terms of genome organization appears to be much larger than previously assumed.

ABSTRACT Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ' ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the “rule of six.” However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily Orthoparamyxovirinae ) and another characterized by CG repeats every 6 nts (observed in the subfamilies Avulavirinae and Rubulavirinae ). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that PE2 of the Rubulavirinae , with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the Rubulavirinae are the only paramyxoviruses that cannot propagate without RNA editing. Filoviruses have three to eight consecutive uracil repeats every six bases (UN 5 ) in PE2, which is located in the 3 ' end region of the genome. We obtained PE2 sequences from 2,195 filoviruses in a public database and analyzed the sequence conservation among virus species. Our results indicate that the continuity of UN 5 hexamers is consistently maintained with a high degree of conservation across virus species. IMPORTANCE The genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters—promoter element 1 (PE1) and promoter element 2 (PE2)—at their 3 ' termini. The spacer region between these elements follows the “rule of six,” crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to Orthoparamyxovirinae and Avulavirinae / Rubulavirinae , respectively, mirroring their evolutionary lineages. Notably, the PE2 of Rubulavirinae is integrated into the gene-coding region, a unique trait potentially linked to its strict dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. The strict conservation of the continuity of UN 5 among virus species emphasizes its crucial role in viral genome replication.

AbstractAs part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxovirus sequences sampled primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirid genomes sequenced from the Americas, including two that are the first full-length bat morbillivirus genome sequences published to date. Our findings add to the vast number of viral sequences in public repositories, which have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PAASC), we propose that five of these sequences belong to members of the genus Jeilongvirus and two belong to members of the genus Morbillivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mòjiāng virus using the same demarcation criteria and suggest reclassification of these viruses into new genera. Importantly, this study underscores the critical importance of sequence length in PAASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences.

Le virus Nipah (NiV) est un virus à ARN à polarité négative non segmenté appartenant à la famille des Paramyxoviridae. Le génome de NiV ne comporte que 6 gènes, mais code pour 9 protéines différentes. Plusieurs protéines sont exprimées à partir du gène P dont la phosphoprotéine P et la protéine C. La protéine C est exprimée à partir d'un cadre de lecture ouvert alternatif par un mécanisme du balayage fuyant ribosomique. La protéine C joue un rôle encore mal compris dans la réplication virale. Pour étudier sa fonction, de nombreuses recherches ont été réalisées en caractérisant un virus recombinant déficient dans l’expression de C (rNiV CKO) où les codons initiateurs de C ont été supprimés, sans toutefois altérer les autres cadres de lecture des protéines issues du gène P. Nous avons émis l’hypothèse que l’absence du site d’initiation de la traduction de C n’empêche pas le mécanisme de balayage ribosomal déficient mais que ces mutations entraînent une désorganisation de l’expression des protéines exprimées à partir du gène P. Nous avons confirmé cette hypothèse en démontrant que le virus rNiV CKO, exprime des formes tronquées des protéines C et P, nommées C’ et P’ respectivement. Par ailleurs, notre évaluation comparative des virus rNiV CKO et NiV sauvage (WT) a révélé que le rNiV CKO produit des particules virales moins infectieuses supposant ainsi un impact des protéines C, C’ et P’ sur la réplication virale. Nous avons développé un système de minigénome NiV et étudié l’effet de ces protéines sur l’activité de la polymérase virale de ce système. C et C' ont montré une régulation négative de l'activité de la polymérase, avec une régulation plus marquée par C'. De plus, nous avons observé des différences de localisation cellulaire entre C et C', cette dernière se localisant dans les corps d'inclusion en présence de protéines virales impliquées dans la synthèse de l'ARN. Concernant la protéine P’, bien qu'elle ait perdu sa fonction principale de liaison aux nucléoprotéines monomériques, aucun effet dominant négatif n'a été observé sur l'activité de la polymérase NiV. De surcroît, un mélange de P’ et de P dépourvues de leur domaine C-terminal Px peut efficacement substituer la P sauvage dans le système de minigénome, offrant ainsi de nouvelles clés de compréhension sur le mécanisme de réplication du NiV. En conclusion, nos résultats suggèrent que l'organisation de l'expression du gène P est complexe, notamment en raison de deux exigences interdépendantes : la synthèse de C dépend d'une initiation faible de la traduction de P, et l’initiation de la traduction de la protéine C est nécessaire pour prévenir une expression potentiellement aberrante de formes tronquées de C et de P
The Nipah virus (NiV) is a non-segmented negative-sense RNA virus belonging to the Paramyxoviridae family. The NiV genome contains only 6 genes but codes for 9 different proteins. Several proteins are expressed from the P gene, including the phosphoprotein P and the C protein. The C protein, expressed from an alternative open reading frame through a ribosomal leaky scanning mechanism, plays a yet poorly understood role in viral replication. To study its function, numerous studies have been conducted on a recombinant NiV deficient in C expression (rNiV CKO), where the initiator codons of C have been removed, without altering other reading frames of the proteins derived from the P gene. We hypothesized that the absence of the C translation initiation site does not prevent the ribosomal leaky scanning mechanism but that these mutations lead to a disorganization of the expression of proteins derived from the P gene. We confirmed this hypothesis by demonstrating that rNiV CKO expresses truncated forms of the C and P proteins, named respectively C’ and P’. Furthermore, our comparative evaluation of rNiV CKO and wild-type NiV (WT) revealed that rNiV CKO produces less infectious viral particles, which directed our research towards the impact of C, C', and P' proteins on viral replication. We developed a NiV minigenome system and studied the effect of these proteins on the viral polymerase activity in this system. C and C' showed negative regulation of polymerase activity, with a more pronounced regulation by C'. Additionally, we observed differences in cellular localization between C and C', with the latter localizing in inclusion bodies in the presence of viral proteins involved in RNA synthesis. Regarding the P' protein, although it lost its primary function of binding to monomeric nucleoproteins, no dominant negative effect was observed on NiV polymerase activity. Moreover, a mixture of P’ and P lacking their C-terminal Px domain can effectively substitute for wild-type P in the minigenome system, providing new insights into the NiV replication mechanism. In conclusion, our results collectively suggest that the organization of P gene expression is complex, likely due to two interdependent requirements: the synthesis of C depends on weak initiation of P translation, and the translation initiation of C protein is necessary to prevent potentially aberrant expression of truncated forms of C and P