RESUMO
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 (UN5) 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 UN5 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 UN5 among virus species emphasizes its crucial role in viral genome replication.
Assuntos
Filoviridae , Genoma Viral , Filogenia , Regiões Promotoras Genéticas , Regiões Promotoras Genéticas/genética , Genoma Viral/genética , Filoviridae/genética , Filoviridae/classificação , Paramyxoviridae/genética , Paramyxoviridae/classificação , Humanos , RNA Viral/genética , Evolução Molecular , AnimaisRESUMO
Ebolaviruses and marburgviruses are filoviruses that are known to cause severe hemorrhagic fever in humans and nonhuman primates (NHPs). While some bat species are suspected to be natural reservoirs of these filoviruses, wild NHPs often act as intermediate hosts for viral transmission to humans. Using an enzyme-linked immunosorbent assay, we screened two NHP species, wild baboons and vervet monkeys captured in Zambia, for their serum IgG antibodies specific to the envelope glycoproteins of filoviruses. From 243 samples tested, 39 NHPs (16%) were found to be seropositive either for ebolaviruses or marburgviruses with endpoint antibody titers ranging from 100 to 25,600. Interestingly, antibodies reactive to Reston virus, which is found only in Asia, were detected in both NHP species. There was a significant difference in the seropositivity for the marburgvirus antigen between the two NHP species, with baboons having a higher positive rate. These results suggest that wild NHPs in Zambia might be nonlethally exposed to these filoviruses, and this emphasizes the need for continuous monitoring of filovirus infection in wild animals to better understand the ecology of filoviruses and to assess potential risks of outbreaks in humans in previously nonendemic countries.
Assuntos
Anticorpos Antivirais/sangue , Infecções por Filoviridae/imunologia , Infecções por Filoviridae/veterinária , Filoviridae/imunologia , Primatas/virologia , Animais , Animais Selvagens/virologia , Chlorocebus aethiops/virologia , Ebolavirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Filoviridae/classificação , Filoviridae/isolamento & purificação , Infecções por Filoviridae/epidemiologia , Humanos , Imunoglobulina G/sangue , Masculino , Marburgvirus/imunologia , Papio/virologia , Estudos Soroepidemiológicos , Zâmbia/epidemiologiaRESUMO
In recent years, a number of novel filoviruses (e.g. Lloviu virus (LLOV) and Bombali virus (BOMV)) have been discovered. While antibody-based therapeutics have recently been approved for treatment of infections with the filovirus Ebola virus (EBOV), no treatment options for novel filoviruses currently exist. Further, the development of antivirals against them is complicated by the fact that only sequence information, but no actual virus isolates, are available. To address this issue, we developed a reverse genetics-based minigenome system for BOMV, which allows us to assess the activity of the BOMV polymerase. Together with similar systems that we have developed for other filoviruses in the past (i.e. LLOV and Reston virus (RESTV)), we then assessed the efficiency of remdesivir, a known inhibitor of the EBOV polymerase that has recently been tested in a clinical trial for efficacy against Ebola disease. We show that remdesivir is indeed also active against the polymerases of BOMV, LLOV, and RESTV, with comparable IC50 values to its activity against EBOV. This suggests that treatment with remdesivir might represent a viable option in case of infections with novel filoviruses.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Filoviridae/efeitos dos fármacos , RNA Polimerase Dependente de RNA/antagonistas & inibidores , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Linhagem Celular , Ebolavirus/efeitos dos fármacos , Filoviridae/classificação , Filoviridae/genética , Humanos , Concentração Inibidora 50 , Filogenia , Replicação Viral/efeitos dos fármacosRESUMO
Ebolaviruses and marburgviruses, members of the family Filoviridae, are known to cause fatal diseases often associated with hemorrhagic fever. Recent outbreaks of Ebola virus disease in West African countries and the Democratic Republic of the Congo have made clear the urgent need for the development of therapeutics and vaccines against filoviruses. Using replication-incompetent vesicular stomatitis virus (VSV) pseudotyped with the Ebola virus (EBOV) envelope glycoprotein (GP), we screened a chemical compound library to obtain new drug candidates that inhibit filoviral entry into target cells. We discovered a biaryl sulfonamide derivative that suppressed in vitro infection mediated by GPs derived from all known human-pathogenic filoviruses. To determine the inhibitory mechanism of the compound, we monitored each entry step (attachment, internalization, and membrane fusion) using lipophilic tracer-labeled ebolavirus-like particles and found that the compound efficiently blocked fusion between the viral envelope and the endosomal membrane during cellular entry. However, the compound did not block the interaction of GP with the Niemann-Pick C1 protein, which is believed to be the receptor of filoviruses. Using replication-competent VSVs pseudotyped with EBOV GP, we selected escape mutants and identified two EBOV GP amino acid residues (positions 47 and 66) important for the interaction with this compound. Interestingly, these amino acid residues were located at the base region of the GP trimer, suggesting that the compound might interfere with the GP conformational change required for membrane fusion. These results suggest that this biaryl sulfonamide derivative is a novel fusion inhibitor and a possible drug candidate for the development of a pan-filovirus therapeutic.
Assuntos
Filoviridae/efeitos dos fármacos , Sulfonamidas/química , Sulfonamidas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Animais , Chlorocebus aethiops , Descoberta de Drogas , Ebolavirus/efeitos dos fármacos , Filoviridae/classificação , Infecções por Filoviridae/tratamento farmacológico , Infecções por Filoviridae/virologia , Células HEK293 , Doença pelo Vírus Ebola/tratamento farmacológico , Humanos , Doença do Vírus de Marburg/tratamento farmacológico , Marburgvirus/efeitos dos fármacos , Receptores Virais/metabolismo , Células VeroRESUMO
Southern China is a hot spot of emerging infectious diseases, in which diverse species of bats dwell, a large group of flying mammals considered natural reservoirs for zoonotic viruses. Recently, divergent filoviruses (FiVs) have been identified in bats within this region, which pose a potential risk to public health, but the true infection situation in bats remains largely unclear. Here, 689 archived bat serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA), Western blotting, and neutralization assay to investigate the seroprevalence and cross-reactivity of four divergent FiVs and two other viruses (rabies virus and Tuhoko pararubulavirus 1) of different families within the order Mononegavirales Results showed no cross-antigenicity between FiVs and other mononegaviruses but different cross-reactivity among the FiVs themselves. The total FiV seroreactive rate was 36.3% (250/689), with infection by the indigenous Chinese FiV DH04 or an antigenically related one being the most widely and the most highly prevalent. Further viral metagenomic analysis of fruit bat tissues also identified the gene sequence of a novel FiV. These results indicate the likely prevalence of other so far unidentified FiVs within the Chinese bat population, with frugivorous Rousettus leschenaultii and Eonycteris spelaea bats and insectivorous Myotis horsfieldii and Miniopterus schreibersii bats being their major reservoirs.IMPORTANCE Bats are natural hosts of many FiVs, from which diverse FiVs were serologically or virologically detected in Africa, Europe, and East Asia. Recently, very divergent FiVs were identified in the Chinese bat population, but their antigenic relationship with other known FiVs remains unknown. Here, we conducted serological characterization and investigation of Chinese indigenous FiVs and prototypes of other viruses in bats. Results indicated that Chinese indigenous FiVs are antigenically distant to other FiVs, and infection of novel or multiple FiVs occurred in Chinese bats, with FiV DH04 or an antigenically related one being the most widely and the most highly prevalent. Additionally, besides Rousettus leschenaultii and Eonycteris spelaea bats, the insectivorous Myotis horsfieldii and M. schreibersii bats are highly preferential hosts of FiVs. Seroreactive and viral metagenomic results indicated that more as yet unknown bat-borne FiVs circulate in Southern China, and to uncover them further, investigation and timely surveillance is needed.
Assuntos
Anticorpos Antivirais/sangue , Quirópteros/virologia , Infecções por Filoviridae/veterinária , Filoviridae/imunologia , Animais , China , Quirópteros/sangue , Coinfecção , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Ensaio de Imunoadsorção Enzimática , Filoviridae/classificação , Metagenômica , Testes de Neutralização , Paramyxoviridae , Infecções por Paramyxoviridae/sangue , Infecções por Paramyxoviridae/veterinária , Filogenia , Rhabdoviridae , Infecções por Rhabdoviridae/sangue , Infecções por Rhabdoviridae/veterinária , Estudos SoroepidemiológicosRESUMO
Bats are reservoirs for several zoonotic pathogens, including filoviruses. Recent work highlights the diversity of bat borne filoviruses in Asia. High risk activities at the bat-human interface pose the threat of zoonotic virus transmission. We present evidence for prior exposure of bat harvesters and two resident fruit bat species to filovirus surface glycoproteins by screening sera in a multiplexed serological assay. Antibodies reactive to two antigenically distinct filoviruses were detected in human sera and to three individual filoviruses in bats in remote Northeast India. Sera obtained from Eonycteris spelaea bats showed similar patterns of cross-reactivity as human samples, suggesting them as the species responsible for the spillover. In contrast, sera from Rousettus leschenaultii bats reacted to two different virus glycoproteins. Our results indicate circulation of several filoviruses in bats and the possibility for filovirus transmission from bats to humans.
Assuntos
Anticorpos Antivirais/sangue , Quirópteros/imunologia , Quirópteros/virologia , Reservatórios de Doenças/virologia , Infecções por Filoviridae/epidemiologia , Infecções por Filoviridae/veterinária , Filoviridae/imunologia , Adolescente , Adulto , Animais , Quirópteros/sangue , Ebolavirus/imunologia , Filoviridae/classificação , Filoviridae/isolamento & purificação , Infecções por Filoviridae/imunologia , Infecções por Filoviridae/virologia , Mapeamento Geográfico , Glicoproteínas/imunologia , Humanos , Índia/epidemiologia , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Filogenia , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense RNA genomes of 15-19 kb. Several filoviruses (e.g., Ebola virus) are pathogenic for humans and are highly virulent. Several filoviruses infect bats (e.g., Marburg virus), whereas the hosts of most other filoviruses are unknown. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on Filoviridae, which is available at www.ictv.global/report/filoviridae.
Assuntos
Filoviridae/classificação , Animais , Filoviridae/genética , Genoma Viral/genética , Humanos , RNA Viral/genéticaRESUMO
Filoviruses, especially Ebola virus (EBOV) and Marburg virus (MARV), are notoriously pathogenic and capable of causing severe haemorrhagic fever diseases in humans with high lethality1,2. The risk of future outbreaks is exacerbated by the discovery of other bat-borne filoviruses of wide genetic diversity globally3-5. Here we report the characterization of a phylogenetically distinct bat filovirus, named Menglà virus (MLAV). The coding-complete genome of MLAV shares 32-54% nucleotide sequence identity with known filoviruses. Phylogenetic analysis places this new virus between EBOV and MARV, suggesting the need for a new genus taxon. Importantly, despite the low amino acid sequence identity (22-39%) of the glycoprotein with other filoviruses, MLAV is capable of using the Niemann-Pick C1 (NPC1) as entry receptor. MLAV is also replication-competent with chimeric MLAV mini-genomes containing EBOV or MARV leader and trailer sequences, indicating that these viruses are evolutionally and functionally closely related. Finally, MLAV glycoprotein-typed pseudo-types transduced cell lines derived from humans, monkeys, dogs, hamsters and bats, implying a broad species cell tropism with a high risk of interspecies spillover transmission.
Assuntos
Quirópteros/virologia , Filoviridae/classificação , Filoviridae/isolamento & purificação , Genoma Viral , Animais , Linhagem Celular , Cricetinae , Cães , Ebolavirus/classificação , Glicoproteínas/genética , Humanos , Marburgvirus/classificação , Proteína C1 de Niemann-Pick/metabolismo , Filogenia , Transdução Genética , Tropismo Viral , Internalização do VírusRESUMO
Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild self-limiting febrile illness to severe disease characterized by high fever, high-level viraemia, increased vascular permeability that can progress to shock, multi-organ failure and death. Despite the urgent need, effective treatments and preventative vaccines are currently lacking for the majority of these viruses. A number of factors preclude the effective study of these diseases in humans including the high virulence of the agents involved, the sporadic nature of outbreaks of these viruses, which are typically in geographically isolated areas with underserviced diagnostic capabilities, and the requirements for high level bio-containment. As a result, animal models that accurately mimic human disease are essential for advancing our understanding of the pathogenesis of viral haemorrhagic fevers. Moreover, animal models for viral haemorrhagic fevers are necessary to test vaccines and therapeutic intervention strategies. Here, we present an overview of the animal models that have been established for each of the haemorrhagic fever viruses and identify which aspects of human disease are modelled. Furthermore, we discuss how experimental design considerations, such as choice of species and virus strain as well as route and dose of inoculation, have an influence on animal model development. We also bring attention to some of the pitfalls that need to be avoided when extrapolating results from animal models.
Assuntos
Modelos Animais de Doenças , Febres Hemorrágicas Virais/patologia , Febres Hemorrágicas Virais/virologia , Animais , Arenaviridae/classificação , Arenaviridae/patogenicidade , Bunyaviridae/classificação , Bunyaviridae/patogenicidade , Filoviridae/classificação , Filoviridae/patogenicidade , Flaviviridae/classificação , Flaviviridae/patogenicidade , Febres Hemorrágicas Virais/fisiopatologia , HumanosAssuntos
Quirópteros/virologia , Doenças Transmissíveis Emergentes/veterinária , Infecções por Filoviridae/veterinária , Filoviridae/isolamento & purificação , Animais , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Filoviridae/classificação , Filoviridae/genética , Infecções por Filoviridae/epidemiologia , Infecções por Filoviridae/patologia , Infecções por Filoviridae/virologia , Hungria/epidemiologia , Pulmão/patologia , Pulmão/virologia , FilogeniaRESUMO
The Filoviridae are a family of negative-strand RNA viruses that include several important human pathogens. Ebola virus (EBOV) and Marburg virus are well-known filoviruses which cause life-threatening viral hemorrhagic fever in human and nonhuman primates. In addition to severe pathogenesis, filoviruses also exhibit a propensity for human-to-human transmission by close contact, posing challenges to containment and crisis management. Past outbreaks, in particular the recent West African EBOV epidemic, have been responsible for thousands of deaths and vaulted the filoviruses into public consciousness. Both national and international health agencies continue to regard potential filovirus outbreaks as critical threats to global public health. To develop effective countermeasures, a basic understanding of filovirus biology is needed. This review encompasses the epidemiology, ecology, molecular biology, and evolution of the filoviruses.
Assuntos
Evolução Biológica , Ecologia , Infecções por Filoviridae/virologia , Filoviridae/classificação , Filoviridae/genética , Filogenia , Animais , Infecções por Filoviridae/transmissão , Genoma Viral/genética , Humanos , Proteínas Virais/genética , Replicação Viral/fisiologiaRESUMO
There are no approved medications for the treatment of Marburg or Ebola virus infection. In two previous articles (Martin et al., 2016, Martin et al., 2017), we reviewed surface glycoprotein and replication proteins structure/function relationship to decipher the molecular mechanisms of filovirus life cycle and identify antiviral strategies. In the present article, we recapitulate knowledge about the viral proteins involved in filovirus assembly and budding. First we describe the structural data available for viral proteins associated with virus assembly and virion egress and then, we integrate the structural features of these proteins in the functional context of the viral replication cycle. Finally, we summarize recent advances in the development of innovative antiviral strategies to target filovirus assembly and egress. The development of such prophylactic or post-exposure treatments could help controlling future filovirus outbreaks.
Assuntos
Antivirais/farmacologia , Descoberta de Drogas , Filoviridae/efeitos dos fármacos , Filoviridae/fisiologia , Proteínas Virais/química , Proteínas Virais/metabolismo , Montagem de Vírus/efeitos dos fármacos , Liberação de Vírus/efeitos dos fármacos , Antivirais/química , Descoberta de Drogas/métodos , Filoviridae/classificação , Genoma Viral , Genômica/métodos , Humanos , Relação Estrutura-Atividade , Proteínas Virais/antagonistas & inibidoresRESUMO
BACKGROUND: Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest. METHODOLOGY/PRINCIPAL FINDING: We have adapted EvoPrinter alignment algorithms for the rapid comparative analysis of Flavivirus or Filovirus sequences including Zika and Ebola strains. The user can input a full genome or partial viral sequence and then view either individual comparisons or generate color-coded readouts that superimpose hundreds of one-on-one alignments to identify unique or shared identity SNPs that reveal ancestral relationships between strains. The user can also opt to select a database genome in order to access a library of pre-aligned genomes of either 1,094 Flaviviruses or 460 Filoviruses for rapid comparative analysis with all database entries or a select subset. Using EvoPrinter search and alignment programs, we show the following: 1) superimposing alignment data from many related strains identifies lineage identity SNPs, which enable the assessment of sublineage complexity within viral outbreaks; 2) whole-genome SNP profile screens uncover novel Dengue2 and Zika recombinant strains and their parental lineages; 3) differential SNP profiling identifies host cell A-to-I hyper-editing within Ebola and Marburg viruses, and 4) hundreds of superimposed one-on-one Ebola genome alignments highlight ultra-conserved regulatory sequences, invariant amino acid codons and evolutionarily variable protein-encoding domains within a single genome. CONCLUSIONS/SIGNIFICANCE: EvoPrinter allows for the assessment of lineage complexity within Flavivirus or Filovirus outbreaks, identification of recombinant strains, highlights sequences that have undergone host cell A-to-I editing, and identifies unique input and database SNPs within highly conserved sequences. EvoPrinter's ability to superimpose alignment data from hundreds of strains onto a single genome has allowed us to identify unique Zika virus sublineages that are currently spreading in South, Central and North America, the Caribbean, and in China. This new set of integrated alignment programs should serve as a useful addition to existing tools for the comparative analysis of these viruses.
Assuntos
Biologia Computacional/métodos , Filoviridae/classificação , Filoviridae/genética , Flavivirus/classificação , Flavivirus/genética , Alinhamento de Sequência/métodos , Animais , Evolução Molecular , Humanos , Epidemiologia Molecular/métodosRESUMO
The International Committee on Taxonomy of Viruses (ICTV) currently recognizes three genera and seven species as part of the mononegaviral family Filoviridae. Eight distinct filoviruses (Bundibugyo virus, Ebola virus, Lloviu virus, Marburg virus, Ravn virus, Reston virus, Sudan virus, and Taï Forest virus) have been assigned to these seven species. This chapter briefly summarizes the status quo of filovirus classification and focuses on the importance of differentiating between filoviral species and filoviruses and the correct use of taxonomic and vernacular filovirus names and abbreviations in written and oral discourse.
Assuntos
Filoviridae/classificação , Terminologia como Assunto , Ebolavirus/classificação , Marburgvirus/classificaçãoRESUMO
The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion characteristics. Here we report filovirus genome sequence-based taxon demarcation criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool of the US National Center for Biotechnology Information (Bethesda, MD, USA). Comparison of all available filovirus genomes in GenBank using PASC revealed optimal genus demarcation at the 55-58% sequence diversity threshold range for genera and at the 23-36% sequence diversity threshold range for species. Because these thresholds do not change the current official filovirus classification, these values are now implemented as filovirus taxon demarcation criteria that may solely be used for filovirus classification in case additional data are absent. A near-complete, coding-complete, or complete filovirus genome sequence will now be required to allow official classification of any novel "filovirus." Classification of filoviruses into existing taxa or determining the need for novel taxa is now straightforward and could even become automated using a presented algorithm/flowchart rooted in RefSeq (type) sequences.
Assuntos
Filoviridae/classificação , Filoviridae/genética , Filogenia , Algoritmos , Sequência de Bases , Bases de Dados de Ácidos Nucleicos , Ebolavirus/classificação , Ebolavirus/genética , Variação Genética , Genoma Viral , Marburgvirus/classificação , Marburgvirus/genética , Mononegavirais/classificação , Mononegavirais/genética , Análise de Sequência de DNA , Design de Software , Especificidade da Espécie , Sequenciamento Completo do GenomaRESUMO
A detailed understanding of the circulating pathogens in a particular geographic location aids in effectively utilizing targeted, rapid diagnostic assays, thus allowing for appropriate therapeutic and containment procedures. This is especially important in regions prevalent for highly pathogenic viruses co-circulating with other endemic pathogens such as the malaria parasite. The importance of biosurveillance is highlighted by the ongoing Ebola virus disease outbreak in West Africa. For example, a more comprehensive assessment of the regional pathogens could have identified the risk of a filovirus disease outbreak earlier and led to an improved diagnostic and response capacity in the region. In this context, being able to rapidly screen a single sample for multiple pathogens in a single tube reaction could improve both diagnostics as well as pathogen surveillance. Here, probes were designed to capture identifying filovirus sequence for the ebolaviruses Sudan, Ebola, Reston, Taï Forest, and Bundibugyo and the Marburg virus variants Musoke, Ci67, and Angola. These probes were combined into a single probe panel, and the captured filovirus sequence was successfully identified using the MiSeq next-generation sequencing platform. This panel was then used to identify the specific filovirus from nonhuman primates experimentally infected with Ebola virus as well as Bundibugyo virus in human sera samples from the Democratic Republic of the Congo, thus demonstrating the utility for pathogen detection using clinical samples. While not as sensitive and rapid as real-time PCR, this panel, along with incorporating additional sequence capture probe panels, could be used for broad pathogen screening and biosurveillance.
Assuntos
Sondas de DNA/síntese química , Ebolavirus/genética , Filoviridae/genética , Doença pelo Vírus Ebola/veterinária , Reação em Cadeia da Polimerase/métodos , RNA Viral/genética , Animais , DNA Complementar/genética , República Democrática do Congo , Ebolavirus/isolamento & purificação , Filoviridae/classificação , Filoviridae/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Humanos , Macaca mulatta , RNA Viral/isolamento & purificação , Análise de Sequência de DNARESUMO
Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information's (NCBI's) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [
Assuntos
Bases de Dados de Ácidos Nucleicos , Filoviridae/genética , Evolução Molecular , Filoviridae/classificação , Humanos , Seleção GenéticaRESUMO
Filoviruses, including Ebolavirus and Marburgvirus, pose significant threats to public health and species conservation by causing hemorrhagic fever outbreaks with high mortality rates. Since the first outbreak in 1967, their origins, natural history, and ecology remained elusive until recent studies linked them through molecular, serological, and virological studies to bats. We review the ecology, epidemiology, and natural history of these systems, drawing on examples from other bat-borne zoonoses, and highlight key areas for future research. We compare and contrast results from ecological and virological studies of bats and filoviruses with those of other systems. We also highlight how advanced methods, such as more recent serological assays, can be interlinked with flexible statistical methods and experimental studies to inform the field studies necessary to understand filovirus persistence in wildlife populations and cross-species transmission leading to outbreaks. We highlight the need for a more unified, global surveillance strategy for filoviruses in wildlife, and advocate for more integrated, multi-disciplinary approaches to understand dynamics in bat populations to ultimately mitigate or prevent potentially devastating disease outbreaks.
Assuntos
Quirópteros/virologia , Infecções por Filoviridae/veterinária , Filoviridae/isolamento & purificação , Zoonoses/epidemiologia , Zoonoses/virologia , Animais , Filoviridae/classificação , Infecções por Filoviridae/epidemiologia , Infecções por Filoviridae/transmissão , Infecções por Filoviridae/virologia , Humanos , Zoonoses/transmissãoRESUMO
The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.