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1.
Antiviral Res ; 209: 105490, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521633

RESUMO

Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues.


Assuntos
Paramyxoviridae , Cricetinae , Animais , Humanos , Mesocricetus , Paramyxoviridae/fisiologia , Modelos Animais , Modelos Animais de Doenças
2.
Viruses ; 14(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36423137

RESUMO

Newcastle disease (ND) is a highly contagious viral disease of poultry causing significant economic losses worldwide. Vaccination is considered the most reliable approach to curb the economic menace that is ND, but the thermolabile nature of Newcastle disease virus (NDV) vaccination poses a significant threat to its protective efficacy. This study aimed to profile the thermostability of NDV isolates from duck (As/Km/19/44) and parrot (As/WB/19/91) and evaluate their immunogenic potential in chicks. Fusion protein cleavage site (FPCS) and phylogenetic analysis demonstrated the lentogenic nature of both the isolates/strains and classified them as class II genotype II NDV. The characterized NDV isolates were adapted in specific-pathogen-free (SPF) chicks by serially passaging. Biological pathogenicity assessment of chicken-adapted As/Km/19/44 (PSD44C) and As/WB/19/91 (PSP91C) revealed both the isolates to be avirulent with a mean death time (MDT) of more than 90 h and an intracerebral pathogenicity index (ICPI) ranging from 0.2 to 0.4. Both of the NDV isolates displayed varied thermostability profiles. PSD44C was the most thermostable strain as compared to PSP91C and the commercially available LaSota vaccine strain. The immunogenicity of PSD44C and LaSota was significantly higher than PSP91C. Based on these results, it is concluded that NDV isolate PSD44C is more thermostable and immunogenic when administered intraocularly without any adverse effects. Therefore, PSD44C is suitable for further research and vaccine development.


Assuntos
Doença de Newcastle , Papagaios , Animais , Patos , Galinhas , Filogenia , Vírus da Doença de Newcastle/genética , Doença de Newcastle/prevenção & controle , Genótipo , Paramyxoviridae
3.
Front Immunol ; 13: 970750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045682

RESUMO

Retinoic acid-inducible gene I (RIG-I) is a receptor that senses viral RNA and interacts with mitochondrial antiviral signaling (MAVS) protein, leading to the production of type I interferons and inflammatory cytokines to establish an antiviral state. This signaling axis is initiated by the K63-linked RIG-I ubiquitination, mediated by E3 ubiquitin ligases such as TRIM25. However, many viruses, including several members of the family Paramyxoviridae and human respiratory syncytial virus (HRSV), a member of the family Pneumoviridae, escape the immune system by targeting RIG-I/TRIM25 signaling. In this study, we screened human metapneumovirus (HMPV) open reading frames (ORFs) for their ability to block RIG-I signaling reconstituted in HEK293T cells by transfection with TRIM25 and RIG-I CARD (an N-terminal CARD domain that is constitutively active in RIG-I signaling). HMPV M2-2 was the most potent inhibitor of RIG-I/TRIM25-mediated interferon (IFN)-ß activation. M2-2 silencing induced the activation of transcription factors (IRF and NF-kB) downstream of RIG-I signaling in A549 cells. Moreover, M2-2 inhibited RIG-I ubiquitination and CARD-dependent interactions with MAVS. Immunoprecipitation revealed that M2-2 forms a stable complex with RIG-I CARD/TRIM25 via direct interaction with the SPRY domain of TRIM25. Similarly, HRSV NS1 also formed a stable complex with RIG-I CARD/TRIM25 and inhibited RIG-I ubiquitination. Notably, the inhibitory actions of HMPV M2-2 and HRSV NS1 are similar to those of V proteins of several members of the Paramyxoviridae family. In this study, we have identified a novel mechanism of immune escape by HMPV, similar to that of Pneumoviridae and Paramyxoviridae family members.


Assuntos
Interferon Tipo I , Metapneumovirus , Infecções por Paramyxoviridae/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Antivirais , Proteína DEAD-box 58/metabolismo , Células HEK293 , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Interferon beta/metabolismo , Paramyxoviridae , Infecções por Paramyxoviridae/virologia , Receptores Imunológicos/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
4.
Arch Virol ; 167(10): 1977-1987, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35781557

RESUMO

As 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 Mòjiang 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.


Assuntos
Quirópteros , Morbillivirus , Vírus , Animais , Brasil , Genoma Viral , Humanos , Malásia , Morbillivirus/genética , Paramyxoviridae/genética , Filogenia
5.
Viruses ; 14(7)2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35891483

RESUMO

Feline morbillivirus (FeMV) is a recently discovered virus belonging to the genus Morbillivirus of the virus family Paramyxoviridae. Often, the virus has been detected in urine of cats with a history of urinary disease and has a worldwide distribution. Currently, it is unclear which receptor the virus uses to enter the target cells. Furthermore, many aspects of FeMV biology in vivo, including tissue tropism, pathogenesis, and virus excretion in the natural host remain unclear. In this study we analyzed the replication of FeMV in various cell lines. Secondly, we tested if the presence of feline SLAMF1 (Signaling Lymphocytic Activation Molecule family 1/CD150, principal entry receptor for other members of the Morbillivirus genus) improved FeMV replication efficiency in vitro. Finally, to elucidate in vivo biology in cats, as a natural host for FeMV, we experimentally infected a group of cats and monitored clinical symptoms, viremia, and excretion of the virus during the course of 56 days. Our study showed that FeMV shares some features with other morbilliviruses like the use of the SLAMF1 receptor. For the first time, experimental infection of SPF cats showed that FeMV does not induce an acute clinical disease like other morbilliviruses but can induce lesions in the kidneys, including tubulointerstitial nephritis. Further investigations are needed to confirm the site and dynamics of replication of FeMV in the urinary tract and the longer-term impact of FeMV-induced lesions on the renal function. Whether FeMV infection can result in chronic kidney disease will require the monitoring of cats over a longer period.


Assuntos
Doenças do Gato , Infecções por Morbillivirus , Morbillivirus , Animais , Doenças do Gato/patologia , Gatos , Rim , Infecções por Morbillivirus/veterinária , Paramyxoviridae
6.
Curr Opin Immunol ; 77: 102209, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35598506

RESUMO

Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture to stabilize it in a vulnerable conformation. We summarize the general principles of structure-based vaccine design, with a focus on the major types of sequence modifications: proline, disulfide, cavity-filling, electrostatic and hydrogen-bond substitution, as well as domain deletion. We then review recent applications of these principles to vaccine-design efforts across five viral families: Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, and Filoviridae. Outstanding challenges include continued application of proven design principles to pathogens of interest, as well as development of new strategies for those pathogens that resist traditional techniques.


Assuntos
Desenvolvimento de Vacinas , Proteínas Virais , Vacinas Virais , Coronaviridae , Filoviridae , Humanos , Orthomyxoviridae , Paramyxoviridae , Pneumovirinae , Proteínas Virais/imunologia , Vacinas Virais/imunologia
7.
Viruses ; 14(5)2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35632848

RESUMO

Paramyxoviridae is a viral family within the order of Mononegavirales; they are negative single-strand RNA viruses that can cause significant diseases in both humans and animals. In order to replicate, paramyxoviruses-as any other viruses-have to bypass an important protective mechanism developed by the host's cells: the defensive line driven by interferon. Once the viruses are recognized, the cells start the production of type I and type III interferons, which leads to the activation of hundreds of genes, many of which encode proteins with the specific function to reduce viral replication. Type II interferon is produced by active immune cells through a different signaling pathway, and activates a diverse range of genes with the same objective to block viral replication. As a result of this selective pressure, viruses have evolved different strategies to avoid the defensive function of interferons. The strategies employed by the different viral species to fight the interferon system include a number of sophisticated mechanisms. Here we analyzed the current status of the various strategies used by paramyxoviruses to subvert type I, II, and III interferon responses.


Assuntos
Paramyxovirinae , Vírus de RNA , Animais , Antivirais , Interferon gama , Interferons , Paramyxoviridae/genética , Vírus de RNA/genética , Replicação Viral
8.
Vopr Virusol ; 67(2): 95-106, 2022 05 05.
Artigo em Russo | MEDLINE | ID: mdl-35521982

RESUMO

Mumps is an infectious disease controlled by specific vaccine prophylaxis. To date, its social and epidemiological significance remains high. This is evidenced by the process of developing and implementing into the health care practices of many countries a set of measures for surveillance of mumps. In the Russian Federation, the National Program «Elimination of measles and rubella and achievement of sporadic morbidity with epidemic mumps in the Russian Federation (2021-2025)¼ and the national plan for its implementation were adopted in 2021. The basis for the adoption of these documents was the development of the domestic trivalent vaccine for the prevention of measles, rubella and mumps, Vaktrivir, and the start of its clinical application. The availability of this vaccine will make the epidemiological surveillance of mumps to be a part of the existing system of appropriate measures for measles and rubella. The fulfillment of this set of tasks involves the study of the molecular epidemiology of the mumps virus (MuV) with possible subsequent implementation of its methodology into the surveillance actions. In this connection, this work was aimed at presenting the data on global genetic diversity of MuV as well as its genotyping methods in a systematized form. The analysis of MuV global genetic diversity in different years will be the starting point in the subsequent development of approach to monitoring virus strains circulating in the Russian Federation.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Variação Genética , Humanos , Lactente , Sarampo/epidemiologia , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/epidemiologia , Caxumba/prevenção & controle , Vacina contra Caxumba , Vírus da Caxumba/genética , Paramyxoviridae , Rubéola (Sarampo Alemão)/prevenção & controle
9.
Viruses ; 14(2)2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-35215881

RESUMO

Paramyxoviruses are a group of RNA viruses, such as mumps virus, measles virus, Nipah virus, Hendra virus, Newcastle disease virus, and parainfluenza virus, usually transmitted by airborne droplets that are predominantly responsible for acute respiratory diseases. In this paper, we identified a novel paramyxovirus belonging to genus Jeilongvirus infecting 4/112 (3.6%) bats from two trapping sites of Hainan Province of China. In these animals, the viral RNA was detected exclusively in kidney tissues. This is the first full-length Jeilongvirus genome (18,095 nucleotides) from bats of genus Hipposideros, which exhibits a canonical genome organization and encodes SH and TM proteins. Results, based on phylogenic analysis and genetic distances, indicate that the novel paramyxovirus formed an independent lineage belonging to genus Jeilongvirus, representing, thus, a novel species. In addition, the virus-host macro-evolutionary analysis revealed that host-switching was not only a common co-phylogenetic event, but also a potential mechanism by which rats are infected by bat-origin Jeilongvirus through cross-species virus transmission, indicating a bat origin of the genus Jeilongvirus. Overall, our study broadens the viral diversity, geographical distribution, host range, and evolution of genus Jeilongvirus.


Assuntos
Coevolução Biológica , Quirópteros/virologia , Paramyxoviridae/genética , Animais , China , Genoma Viral/genética , Especificidade de Hospedeiro , Rim/virologia , Paramyxoviridae/classificação , Filogenia , RNA Viral/genética , Especificidade da Espécie , Proteínas Virais/genética
10.
J Virol ; 96(3): e0109821, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-34668771

RESUMO

Paramyxoviruses are a diverse group of negative-sense, single-stranded RNA viruses of which several species cause significant mortality and morbidity. In recent years the collection of paramyxovirus sequences detected in wild mammals has substantially grown; however, little is known about paramyxovirus diversity in North American mammals. To better understand natural paramyxovirus diversity, host range, and host specificity, we sought to comprehensively characterize paramyxoviruses across a range of diverse cooccurring wild small mammals in southern Arizona. We used highly degenerate primers to screen fecal and urine samples and obtained a total of 55 paramyxovirus sequences from 12 rodent species and 6 bat species. We also performed Illumina transcriptome sequencing (RNA-seq) and de novo assembly on 14 of the positive samples to recover a total of 5 near-full-length viral genomes. We show there are at least two clades of rodent-borne paramyxoviruses in Arizona, while bat-associated paramyxoviruses formed a putative single clade. Using structural homology modeling of the viral attachment protein, we infer that three of the five novel viruses likely bind sialic acid in a manner similar to other respiroviruses, while the other two viruses from heteromyid rodents likely bind a novel host receptor. We find no evidence for cross-species transmission, even among closely related sympatric host species. Taken together, these data suggest paramyxoviruses are a common viral infection in some bat and rodent species present in North America and illuminate the evolution of these viruses. IMPORTANCE There are a number of viral lineages that are potential zoonotic threats to humans. One of these, paramyxoviruses have jumped into humans multiple times from wild and domestic animals. We conducted one of the largest viral surveys of wild mammals in the United States to better understand paramyxovirus diversity and evolution.


Assuntos
Doenças dos Animais/epidemiologia , Doenças dos Animais/virologia , Quirópteros/virologia , Infecções por Paramyxoviridae/veterinária , Paramyxoviridae/classificação , Paramyxoviridae/genética , Sequência de Aminoácidos , Doenças dos Animais/diagnóstico , Animais , Arizona/epidemiologia , Biodiversidade , Evolução Biológica , Genoma Viral , Genômica/métodos , Geografia Médica , Sequenciamento de Nucleotídeos em Larga Escala , Especificidade de Hospedeiro , Humanos , Modelos Moleculares , Técnicas de Diagnóstico Molecular/métodos , América do Norte/epidemiologia , Filogenia , Ligação Proteica , RNA Viral , Receptores Virais/química , Receptores Virais/metabolismo , Respirovirus/classificação , Respirovirus/genética , Infecções por Respirovirus/veterinária , Roedores/virologia
11.
Zoonoses Public Health ; 69(2): 117-135, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34817117

RESUMO

Bat paramyxoviruses (PmV) are a diverse group of viruses and include zoonotic viruses such as henipaviruses. Members of this group in other continents have been associated with severe respiratory and neurological infections in animals and humans. Furthermore, despite the richness of diverse bat species that can transmit this virus in African countries like Nigeria, there is very scanty information as to the presence and co-evolution of paramyxoviruses in bats. There is a need for continuous surveillance of zoonotic viruses and their biological reservoirs as this will help in the prevention and management of pathogens' spillovers. This study detected novel paramyxoviruses in Chaerephon nigeriae bat species found in Badagry, Lagos. Phylogenetic analyses of paramyxovirus sequences' co-evolution with frugivorous and insectivorous bats circulating in African countries were also performed using sequences of African origin available in the Database of Bat-Associated Viruses (DBatVir: http://www.mgc.ac.cn/DBatVir/). Oral swabs (n = 18) and blood samples (n = 32) were collected from C. nigeriae bats in Badagry, Lagos. The L gene of bat paramyxovirus was detected in all oral swabs using PCR techniques. Six of the amplicons were successfully sequenced. Estimated phylogenies placed the sequences in close relationship with those isolated from insectivorous bats. Phylogenetic analyses of previously sequenced isolates in the African region showed the likelihood of different co-evolution mechanisms of paramyxoviruses with frugivorous bats compared with insectivorous bats. This may be due to codon usage bias of the L gene. Spatial distribution of paramyxoviruses in African countries showed limited ongoing surveillance of this virus in the continent, especially in southern and northern countries. Extensive surveillance of paramyxoviruses with possible zoonotic potentials among bat species in the continent is recommended. This will provide further insights into co-evolution as well as prevent possible spillover into the human population.


Assuntos
Quirópteros , Paramyxovirinae , Animais , Nigéria/epidemiologia , Paramyxoviridae/genética , Paramyxovirinae/genética , Filogenia
12.
Viruses ; 15(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36680089

RESUMO

J paramyxovirus (JPV) is a rodent-borne Jeilongvirus isolated from moribund mice (Mus musculus) with hemorrhagic lung lesions trapped in the 1972 in northern Queensland, Australia. The JPV antibodies have been detected in wild mice, wild rats, pigs, and human populations in Australia. Here, by next-generation sequencing (NGS), we detected JPV from M. musculus in Shandong Province of China. Molecular detection of JPV was performed to survey to survey the infection among 66 species of wild small mammals collected from six eco-climate regions in China by applying JPV specific RT-PCR and sequencing. Altogether, 21 out of 3070 (0.68%) wild small mammals of four species were positive for JPV, including 5.26% (1/19) of Microtus fortis, 3.76% (17/452) of M. musculus, 1.67% (1/60) of Apodemus peninsulae, and 0.48% (2/421) of Apodemus agrarius, which captured three eco-climate regions of China (northeastern China, northern China, and Inner Mongolia-Xinjiang). Sequence analysis revealed the currently identified JPV was clustered with other 14 Jeilongvirus members, and shared 80.2% and 89.2% identity with Australia's JPV partial RNA polymerase (L) and glycoprotein (G) genes, respectively. Phylogenetic analysis demonstrated the separation of three lineages of the current JPV sequences. Our results show three new hosts (A. agrarius, A. peninsulae, and M. fortis) for JPV, most of which were widely distributed in China, and highlight the potential zoonotic transmission of JPV in humans. The detection of JPV in wild small mammals in China broaden the viral diversity, geographical distribution, and reservoir types of JPV. Future studies should prioritize determining the epidemiological characteristics of JPV, so that potential risks can be mitigated.


Assuntos
Especificidade de Hospedeiro , Paramyxovirinae , Humanos , Camundongos , Ratos , Animais , Suínos , Filogenia , Paramyxovirinae/genética , Mamíferos , Paramyxoviridae , Murinae , Arvicolinae , Variação Genética , China/epidemiologia
13.
Open Vet J ; 12(6): 868-876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36650879

RESUMO

Paramyxoviruses have been shown to infect a wide range of hosts, including rodents, and humans. Several novel murine paramyxoviruses have been discovered in the last several decades. Although these viruses are unclassified, they are recognized as Beilong virus, Mojiang virus (MojV), and Tailam virus in rats, Jeilongvirus, Nariva, Paju Apodemus paramyxovirus-1 and -2 in mice, and Pentlands paramyxovirus-1, -2, and -3 in squirrels. These paramyxoviruses were reported mainly in China and a few other countries like Australia, the Republic of Korea, Trinidad, and France. In June 2012, it becomes a great concern in China whereby, three miners were reported dead potentially caused by a novel zoonotic MojV, a henipa-like virus isolated from tissue samples of rats from the same cave. Rats are considered to be natural hosts for the MojV from the literature research. The classified paramyxovirus, Sendai virus in rodents is also reviewed. Paramyxoviruses infection in rodents leads to respiratory distress such as necrotizing rhinitis, tracheitis, bronchiolitis, and interstitial pneumonia. Infections caused by paramyxoviruses often spread between species, manifesting disease in spillover hosts, including humans. This review focuses on the paramyxoviruses in rodents, including the epidemiological distributions, transmission and pathogenesis, clinical manifestations, diagnostic methods, and control and prevention of paramyxoviruses infection to provide a better understanding of these highly mutating viruses.


Assuntos
Infecções por Paramyxoviridae , Paramyxovirinae , Doenças dos Roedores , Ratos , Camundongos , Humanos , Animais , Roedores , Paramyxoviridae , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/veterinária , Doenças dos Roedores/epidemiologia
14.
Sci Rep ; 11(1): 24262, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930962

RESUMO

Bat-borne viruses in the Henipavirus genus have been associated with zoonotic diseases of high morbidity and mortality in Asia and Australia. In Africa, the Egyptian rousette bat species (Rousettus aegyptiacus) is an important viral host in which Henipavirus-related viral sequences have previously been identified. We expanded these findings by assessing the viral dynamics in a southern African bat population. A longitudinal study of henipavirus diversity and excretion dynamics identified 18 putative viral species circulating in a local population, three with differing seasonal dynamics, and the winter and spring periods posing a higher risk of virus spillover and transmission. The annual peaks in virus excretion are most likely driven by subadults and may be linked to the waning of maternal immunity and recolonization of the roost in early spring. These results provide insightful information into the bat-host relationship that can be extrapolated to other populations across Africa and be communicated to at-risk communities as a part of evidence-based public health education and prevention measures against pathogen spillover threats.


Assuntos
Quirópteros/virologia , Reservatórios de Doenças/virologia , Marburgvirus/imunologia , Paramyxoviridae/imunologia , Estações do Ano , África , Animais , Ásia , Austrália , Geografia , Henipavirus , Humanos , Estudos Longitudinais , África do Sul , Fatores de Tempo , Zoonoses/epidemiologia , Zoonoses/virologia
15.
PLoS One ; 16(12): e0260360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855795

RESUMO

Recent emergence of SARS-CoV-2 and associated COVID-19 pandemic have posed a great challenge for the scientific community. In this study, we performed bioinformatic analyses on SARS-CoV-2 protein sequences, trying to unravel potential molecular similarities between this newly emerged pathogen with non-coronavirus ssRNA viruses. Comparing the proteins of SARS-CoV-2 with non-coronavirus positive and negative strand ssRNA viruses revealed multiple sequence similarities between SARS-CoV-2 and non-coronaviruses, including similarities between RNA-dependent RNA-polymerases and helicases (two highly-conserved proteins). We also observed similarities between SARS-CoV-2 surface (i.e. spike) protein with paramyxovirus fusion proteins. This similarity was restricted to a segment of spike protein S2 subunit which is involved in cell fusion. We next analyzed spike proteins from SARS-CoV-2 "variants of concern" (VOCs) and "variants of interests" (VOIs) and found that some of these variants show considerably higher spike-fusion similarity with paramyxoviruses. The 'spike-fusion' similarity was also observed for some pathogenic coronaviruses other than SARS-CoV-2. Epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that several B cell epitopes as well as T cell and MHC binding epitopes map within the spike-fusion similarity region. These data indicate that there might be a degree of convergent evolution between SARS-CoV-2 and paramyxovirus surface proteins which could be of pathogenic and immunological importance.


Assuntos
SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Virais de Fusão/genética , Epitopos/genética , Humanos , Paramyxoviridae/genética , Filogenia , Estrutura Terciária de Proteína , Glicoproteína da Espícula de Coronavírus/química
16.
mBio ; 12(6): e0262121, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34724816

RESUMO

Multiple enveloped RNA viruses of the family Paramyxoviridae and Pneumoviridae, like measles virus (MeV), Nipah virus (NiV), canine distemper virus (CDV), or respiratory syncytial virus (RSV), are of high clinical relevance. Each year a huge number of lives are lost as a result of these viral infections. Worldwide, MeV infection alone is responsible for over a hundred thousand deaths each year despite available vaccine. Therefore, there is an urgent need for treatment options to counteract these viral infections. The development of antiviral drugs in general stands as a huge challenge due to the rapid emergence of viral escape mutants. Here, we disclose the discovery of a small-molecule antiviral, compound 1 (ZHAWOC9045), active against several pneumo-/paramyxoviruses, including MeV, NiV, CDV, RSV, and parainfluenza virus type 5 (PIV-5). A series of mechanistic characterizations revealed that compound 1 targets a host factor which is indispensable for viral genome replication. Drug resistance profiling against a paramyxovirus model (CDV) demonstrated no detectable adaptation despite prolonged time of investigation, thereby mitigating the rapid emergence of escape variants. Furthermore, a thorough structure-activity relationship analysis of compound 1 led to the invention of 100-times-more potent-derivatives, e.g., compound 2 (ZHAWOC21026). Collectively, we present in this study an attractive host-directed pneumoviral/paramyxoviral replication inhibitor with potential therapeutic application. IMPORTANCE Measles virus, respiratory syncytial virus, canine distemper virus, and Nipah virus are some of the clinically significant RNA viruses that threaten substantial number of lives each year. Limited to no availability of treatment options for these viral infections makes it arduous to handle the outbreaks. This highlights the major importance of developing antivirals to fight not only ongoing infections but also potential future epidemics. Most of the discovered antivirals, in clinical trials currently, are virus targeted, which consequently poses the challenge of rapid emergence of escape variants. Here, we present compound 1 (ZHAWOC9045), discovered to target viral replication in a host-dependent manner, thereby exhibiting broad-spectrum activity against several members of the family Pneumo-/Paramyxoviridae. The inability of viruses to mutate against the inhibitor mitigated the critical issue of generation of escape variants. Importantly, compound 1 was successfully optimized to a highly potent variant, compound 2 (ZHAWOC21026), with a promising profile for pharmacological intervention.


Assuntos
Antivirais/farmacologia , Paramyxoviridae/fisiologia , Pneumovirus/fisiologia , Replicação Viral/efeitos dos fármacos , Antivirais/química , Descoberta de Drogas , Humanos , Paramyxoviridae/genética , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Paramyxoviridae/virologia , Pneumovirus/genética , Infecções por Pneumovirus/tratamento farmacológico , Infecções por Pneumovirus/virologia
17.
Microbiol Spectr ; 9(2): e0093021, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34668744

RESUMO

Bats are a reservoir for many zoonotic viruses and host large numbers of genetically diverse species in the families Rhabdoviridae, Coronaviridae, and Paramyxoviridae. Viruses from these families have repeatedly spilled over to humans in recent decades, causing significant clinical disease and deaths. Here, metagenomic sequencing of a big brown bat (Eptesicus fuscus) submitted for rabies testing due to human exposure identified a novel paramyxovirus, Eptesicus fuscus orthorubulavirus (EfORV), in South Dakota, United States. The nearly complete 15,814-nucleotide genome shared 72% identity with that of human parainfluenza virus 4 (HPIV4), a virus that causes significant clinical disease, typically bronchiolitis and pneumonia, in children less than 2 years of age. Phylogenetic analysis confirmed a close evolutionary history between EfORV and HPIV4, reminiscent of other orthorubulaviruses with highly similar bat and mammalian species, including conspecific human and bat mumps virus, mammalian parainfluenza virus 5 and bat Alston virus, and porcine La Piedad Michoacán virus and bat Mapuera virus. These results support the idea that bats are a reservoir for diverse paramyxoviruses with closely shared evolutionary histories, compared with a number of significant human pathogens, and expand the range of bat paramyxoviruses to North America. Given the propensity of paramyxoviruses to overcome species barriers, additional surveillance and characterization of EfORV are warranted. IMPORTANCE Bats are a reservoir of large numbers of viruses. Among bat-borne zoonotic viruses, members of Coronaviridae and Paramyxoviridae have had the largest impact on human health. The repeated spillover of bat viruses to humans, often with devastating results, has led to increased surveillance and virus discovery efforts in hot spots for virus emergence, largely Asia and Africa. Apart from rabies virus, little surveillance of viruses in bats is performed in North America. Here, viral metagenomic sequencing identified a close relative to HPIV4 in a big brown bat found in a motel room in South Dakota. The virus, EfORV, was 72% identical to HPIV4, which causes clinically significant respiratory disease, mainly in children; it represents the first bat paramyxovirus identified in North America. Close genetic relationships between bat and mammalian orthorubulaviruses underscore the importance of bats as a reservoir for zoonotic viruses.


Assuntos
Quirópteros/virologia , Paramyxoviridae/classificação , Paramyxoviridae/isolamento & purificação , Animais , Reservatórios de Doenças/virologia , Genoma Viral/genética , Humanos , Metagenômica , Vírus da Parainfluenza 4 Humana/classificação , Vírus da Parainfluenza 4 Humana/genética , Paramyxoviridae/genética , South Dakota , Zoonoses/virologia
18.
Infect Genet Evol ; 95: 105041, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34411742

RESUMO

Paramyxoviruses have a broad host range and geographic distribution, including human pathogens transmitted by bats, such as Nipah and Hendra viruses. In this study, we combined high-throughput sequencing and molecular approaches to investigate the presence of paramyxoviruses in neotropical bats (Microchiroptera suborder) in Brazil. We discovered and characterized three novel paramyxoviruses in the kidney tissues of apparently healthy common vampire bats (D. rotundus) and Seba's short-tailed bats (C. perspicillata), which we tentatively named Kanhgág virus (KANV), Boe virus (BOEV), and Guató virus (GUATV). In this study, we classified these viruses as putative species into the Macrojêvirus genus, a newly proposed genus of the Orthoparamyxovirinae subfamily. Using RT-PCR, we detected these viruses in 20.9% (9 out of 43) of bats tested, and viral RNA was detected exclusively in kidney tissues. Attempts to isolate infectious virus were successful for KANV and GUATV. Our results expand the viral diversity, host range, and geographical distribution of the paramyxoviruses.


Assuntos
Quirópteros , Infecções por Paramyxoviridae/veterinária , Paramyxoviridae/classificação , Animais , Brasil/epidemiologia , Especificidade de Hospedeiro , Paramyxoviridae/fisiologia , Filogenia , Prevalência , RNA Viral/análise
19.
J Virol ; 95(20): e0103021, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34379508

RESUMO

We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15 to 30 amino acid residues in length, that is added to cargo proteins and that induces them to bind to the viral matrix (M) protein during virus-like particle (VLP) assembly. The cargo is then incorporated within the VLPs as they bud, using the same interactions that normally direct viral genome packaging. The appendage can also serve as an epitope tag for cargo detection using a nucleocapsid (NP) protein-specific monoclonal antibody. Using this approach, we generated Renilla luciferase-loaded VLPs, green fluorescent protein-loaded VLPs, superoxide dismutase-loaded VLPs, and Cre recombinase-loaded VLPs. In each case, the VLPs could efficiently deliver their functional cargos to target cells and, in the case of Cre recombinase, to target cell nuclei. The strategy was employed using two different VLP production platforms, one based on parainfluenza virus 5 (PIV5) and the other based on Nipah virus, and in both cases efficient cargo packaging and delivery could be achieved. These findings provide a foundation for development of paramyxovirus-like particles as tools for safe and efficient delivery of therapeutic proteins to cells and tissues. IMPORTANCE Therapeutic proteins including transcription factors and genome editors have enormous clinical potential but are currently limited in part due to the challenges of safely and efficiently delivering these proteins to the interiors of target cells. Here, we have developed a new strategy for protein delivery based on manipulation of paramyxovirus genome packaging interactions.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Paramyxoviridae/metabolismo , Proteínas da Matriz Viral/metabolismo , Engenharia Genética/métodos , Humanos , Luciferases de Renilla/metabolismo , Nucleocapsídeo/metabolismo , Paramyxoviridae/genética , Vírion/metabolismo , Montagem de Vírus
20.
Virology ; 562: 40-49, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256243

RESUMO

Paramyxoviruses harbored by multiple natural reservoirs pose a potential threat to public health. Jeilongvirus has been proposed as a novel paramyxovirus genus found in rodents, bats, and cats. Paramyxovirus RNA was detected in 108/824 (13.1%) Apodemus agrarius captured at 14 trapping sites in the Republic of Korea. We first present two genetically distinct novel paramyxoviruses, Paju Apodemus paramyxovirus 1 (PAPV-1) and 2 (PAPV-2). The disparity between PAPV-1 (19,716 nucleotides) and -2 (17,475 nucleotides) revealed the presence of the SH gene and length of the G gene in the genome organization. The phylogeny of PAPV-1 and -2 belonged to distinct genetic lineages of Jeilongvirus, respectively, even though these viruses were originated from A. agrarius. PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III interferons, interferon-stimulated genes, and pro-inflammatory cytokines. Therefore, this study provides insights into the molecular epidemiology, genetic diversity, and virus-host interactions of novel rodent-borne paramyxoviruses.


Assuntos
Murinae/virologia , Paramyxoviridae/classificação , Paramyxoviridae/genética , Animais , Citocinas/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Genoma Viral/genética , Humanos , Filogenia , RNA Viral/genética , República da Coreia , Especificidade da Espécie , Proteínas Virais/genética , Replicação Viral
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