RESUMO
Marburg virus (MARV), the causative agent of Marburg virus disease, emerges sporadically in sub-Saharan Africa and is often fatal in humas. The natural reservoir for this zoonotic virus is the frugivorous Egyptian rousette bat (Rousettus aegyptiacus) that when infected, sheds virus in the highest amounts in oral secretions and urine. Being fruit bats, these animals forage nightly for ripened fruit throughout the year, including those types often preferred by humans. During feeding, they continually discard partially eaten fruit on the ground that could then be consumed by other Marburg virus susceptible animals or humans. In this study, using qRT-PCR and virus isolation, we tested fruit discarded by Egyptian rousette bats experimentally infected with a natural bat isolate of Marburg virus. We then separately tested viral persistence on fruit varieties commonly cultivated in sub-Saharan Africa using a recombinant Marburg virus expressing the fluorescent ZsGreen1. Marburg virus RNA was repeatedly detected on fruit in the food bowls of the infected bats and viable MARV was recovered from inoculated fruit for up to 6 h.
Assuntos
Quirópteros/virologia , Frutas/virologia , Marburgvirus/isolamento & purificação , Doenças dos Primatas/virologia , Zoonoses Virais/virologia , África Subsaariana , Animais , Quirópteros/fisiologia , Quirópteros/urina , Reservatórios de Doenças/virologia , Humanos , Marburgvirus/classificação , Marburgvirus/genética , Doenças dos Primatas/transmissão , Primatas , Zoonoses Virais/transmissãoRESUMO
Marburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case-fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats.
Assuntos
Quirópteros/virologia , Marburgvirus/isolamento & purificação , África Ocidental , Animais , Cavernas , Genoma Viral , Geografia , Funções Verossimilhança , Doença do Vírus de Marburg/virologia , Marburgvirus/classificação , Marburgvirus/genética , Filogenia , Análise de Sequência de DNA , Proteínas Virais/metabolismoRESUMO
We detected Marburg virus genome in Egyptian fruit bats (Rousettus aegyptiacus) captured in Zambia in September 2018. The virus was closely related phylogenetically to the viruses that previously caused Marburg outbreaks in the Democratic Republic of the Congo. This finding demonstrates that Zambia is at risk for Marburg virus disease.
Assuntos
Quirópteros/virologia , Doença do Vírus de Marburg/virologia , Marburgvirus , Animais , Genes Virais , Humanos , Doença do Vírus de Marburg/diagnóstico , Doença do Vírus de Marburg/epidemiologia , Marburgvirus/classificação , Marburgvirus/genética , Marburgvirus/isolamento & purificação , Filogenia , Prevalência , Vigilância em Saúde Pública , RNA Viral , Zâmbia/epidemiologiaRESUMO
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
We detected a high seroprevalence of Marburg virus (MARV) antibodies in fruit bats in South Africa; 19.1% of recaptured bats seroconverted. The MARV RNA isolated closely resembled the 1975 Ozolin strain. These findings indicate endemic MARV circulation in bats in South Africa and should inform policies on MARV disease risk reduction.
Assuntos
Quirópteros/virologia , Reservatórios de Doenças/virologia , Doença do Vírus de Marburg/epidemiologia , Doença do Vírus de Marburg/virologia , Marburgvirus , Animais , Genes Virais , História do Século XXI , Doença do Vírus de Marburg/história , Doença do Vírus de Marburg/transmissão , Marburgvirus/classificação , Marburgvirus/genética , Filogenia , Vigilância em Saúde Pública , Estudos Soroepidemiológicos , África do Sul/epidemiologiaRESUMO
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
In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.
Assuntos
Surtos de Doenças , Doença do Vírus de Marburg/epidemiologia , Doença do Vírus de Marburg/prevenção & controle , Marburgvirus/genética , Filogenia , Adulto , Animais , Quirópteros/virologia , Reservatórios de Doenças/virologia , Evolução Fatal , Humanos , Masculino , Marburgvirus/classificação , Marburgvirus/isolamento & purificação , Equipamento de Proteção Individual/estatística & dados numéricos , Uganda/epidemiologiaRESUMO
Marburg virus (MARV) causes severe, often fatal, disease in humans and transient illness in rodents. Sequential passaging of MARV in guinea pigs resulted in selection of a lethal virus containing 4 aa changes. A D184N mutation in VP40 (VP40D184N), which leads to a species-specific gain of viral fitness, and three mutations in the active site of viral RNA-dependent RNA polymerase L, which were investigated in the present study for functional significance in human and guinea pig cells. The transcription/replication activity of L mutants was strongly enhanced by a substitution at position 741 (S741C), and inhibited by other substitutions (D758A and A759D) in both species. The polymerase activity of L carrying the S741C substitution was eightfold higher in guinea pig cells than in human cells upon co-expression with VP40D184N, suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host.
Assuntos
RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Cobaias/virologia , Doença do Vírus de Marburg/virologia , Marburgvirus/enzimologia , Doenças dos Roedores/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Domínio Catalítico , RNA Polimerases Dirigidas por DNA/química , Doença do Vírus de Marburg/mortalidade , Marburgvirus/classificação , Marburgvirus/genética , Marburgvirus/isolamento & purificação , Mutação de Sentido Incorreto , Doenças dos Roedores/mortalidade , Proteínas Virais/químicaRESUMO
According to the WHO, ebolaviruses have resulted in 8818 human deaths in West Africa as of January 2015. To better understand the evolutionary relationship of the ebolaviruses and infer virulence from the relationship, we applied the alignment-free natural vector method to classify the newest ebolaviruses. The dataset includes three new Guinea viruses as well as 99 viruses from Sierra Leone. For the viruses of the family of Filoviridae, both genus label classification and species label classification achieve an accuracy rate of 100%. We represented the relationships among Filoviridae viruses by Unweighted Pair Group Method with Arithmetic Mean (UPGMA) phylogenetic trees and found that the filoviruses can be separated well by three genera. We performed the phylogenetic analysis on the relationship among different species of Ebolavirus by their coding-complete genomes and seven viral protein genes (glycoprotein [GP], nucleoprotein [NP], VP24, VP30, VP35, VP40, and RNA polymerase [L]). The topology of the phylogenetic tree by the viral protein VP24 shows consistency with the variations of virulence of ebolaviruses. The result suggests that VP24 be a pharmaceutical target for treating or preventing ebolaviruses.
Assuntos
Ebolavirus/classificação , Ebolavirus/genética , Evolução Molecular , Genoma Viral , Marburgvirus/classificação , Marburgvirus/genética , Modelos Genéticos , Tipagem Molecular , Filogenia , Análise de Sequência de DNARESUMO
Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.
Assuntos
Doença pelo Vírus Ebola/epidemiologia , Doença do Vírus de Marburg/epidemiologia , África/epidemiologia , Animais , Antivirais/uso terapêutico , Diagnóstico Diferencial , Surtos de Doenças , Reservatórios de Doenças , Ebolavirus/classificação , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/virologia , Humanos , Doença do Vírus de Marburg/mortalidade , Doença do Vírus de Marburg/terapia , Doença do Vírus de Marburg/virologia , Marburgvirus/classificaçãoRESUMO
The Marburg viruses Musoke (MARV-Mus) and Angola (MARV-Ang) have highly similar genomic sequences. Analysis of viral replication using various assays consistently identified MARV-Ang as the faster replicating virus. Non-coding genomic regions of negative sense RNA viruses are known to play a role in viral gene expression. A comparison of the six non-coding regions using bicistronic minigenomes revealed that the first two non-coding regions (NP/VP35 and VP35/VP40) differed significantly in their transcriptional regulation. Deletion mutation analysis of the MARV-Mus NP/VP35 region further revealed that the MARV polymerase (L) is able to initiate production of the downstream gene without the presence of highly conserved regulatory signals. Bicistronic minigenome assays also identified the VP30 mRNA 5' untranslated region as an rZAP-targeted RNA motif. Overall, our studies indicate that the high variation of MARV non-coding regions may play a significant role in observed differences in transcription and/or replication.
Assuntos
Genoma Viral , Marburgvirus/classificação , Marburgvirus/genética , Replicação Viral/genética , Animais , Linhagem Celular , Regulação Viral da Expressão Gênica/fisiologia , Humanos , Marburgvirus/fisiologia , Mutação , Proteínas Virais/genética , Proteínas Virais/metabolismo , Replicação Viral/fisiologiaRESUMO
Viruses in the Ebolavirus and Marburgvirus genera (family Filoviridae) have been associated with large outbreaks of hemorrhagic fever in human and nonhuman primates. The first documented cases occurred in primates over 45 years ago, but the amount of virus genetic diversity detected within bat populations, which have recently been identified as potential reservoir hosts, suggests that the filoviruses are much older. Here, detailed Bayesian coalescent phylogenetic analyses are performed on 97 whole-genome sequences, 55 of which are newly reported, to comprehensively examine molecular evolutionary rates and estimate dates of common ancestry for viruses within the family Filoviridae. Molecular evolutionary rates for viruses belonging to different species range from 0.46 × 10(-4) nucleotide substitutions/site/year for Sudan ebolavirus to 8.21 × 10(-4) nucleotide substitutions/site/year for Reston ebolavirus. Most recent common ancestry can be traced back only within the last 50 years for Reston ebolavirus and Zaire ebolavirus species and suggests that viruses within these species may have undergone recent genetic bottlenecks. Viruses within Marburg marburgvirus and Sudan ebolavirus species can be traced back further and share most recent common ancestors approximately 700 and 850 years before the present, respectively. Examination of the whole family suggests that members of the Filoviridae, including the recently described Lloviu virus, shared a most recent common ancestor approximately 10,000 years ago. These data will be valuable for understanding the evolution of filoviruses in the context of natural history as new reservoir hosts are identified and, further, for determining mechanisms of emergence, pathogenicity, and the ongoing threat to public health.
Assuntos
Ebolavirus/genética , Genoma Viral , Doença pelo Vírus Ebola/genética , Doença do Vírus de Marburg/genética , Marburgvirus/genética , Substituição de Aminoácidos , Animais , Sequência de Bases , Quirópteros/virologia , Ebolavirus/classificação , Evolução Molecular , Variação Genética , Doença pelo Vírus Ebola/epidemiologia , Humanos , Doença do Vírus de Marburg/epidemiologia , Marburgvirus/classificação , Dados de Sequência Molecular , Filogenia , Primatas/virologia , Análise de Sequência de DNA , Proteínas Virais/química , Proteínas Virais/genéticaRESUMO
Sporadic fatal outbreaks of disease in humans and non-human primates caused by Ebola or Marburg viruses have driven research into the characterization of these viruses with the hopes of identifying host tropisms and potential reservoirs. Such an understanding of the relatedness of newly discovered filoviruses may help to predict risk factors for outbreaks of hemorrhagic disease in humans and/or non-human primates. Recent discoveries such as three distinct genotypes of Reston ebolavirus, unexpectedly discovered in domestic swine in the Philippines; as well as a new species, Bundibugyo ebolavirus; the recent discovery of Lloviu virus as a potential new genus, Cuevavirus, within Filoviridae; and germline integrations of filovirus-like sequences in some animal species bring new insights into the relatedness of filoviruses, their prevalence and potential for transmission to humans. These new findings reveal that filoviruses are more diverse and may have had a greater influence on the evolution of animals than previously thought. Herein we review these findings with regard to the implications for understanding the host range, prevalence and transmission of Filoviridae.
Assuntos
Filoviridae/classificação , Filoviridae/genética , Animais , Reservatórios de Doenças/virologia , Ebolavirus/classificação , Ebolavirus/genética , Ebolavirus/patogenicidade , Filoviridae/patogenicidade , Infecções por Filoviridae/transmissão , Infecções por Filoviridae/virologia , Genoma Viral , Humanos , Marburgvirus/classificação , Marburgvirus/genética , Marburgvirus/patogenicidade , Filogenia , Suínos/virologiaRESUMO
Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack.
Assuntos
Adenoviridae/genética , Vacinas contra Ebola , Filoviridae , Vetores Genéticos , Doença pelo Vírus Ebola/prevenção & controle , Doença do Vírus de Marburg/prevenção & controle , Vacinas Virais , Adenoviridae/imunologia , Animais , Antígenos Virais/genética , Antígenos Virais/metabolismo , Bioterrorismo/prevenção & controle , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/genética , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Ebolavirus/patogenicidade , Filoviridae/classificação , Filoviridae/genética , Filoviridae/imunologia , Doença pelo Vírus Ebola/imunologia , Humanos , Macaca fascicularis , Doença do Vírus de Marburg/imunologia , Marburgvirus/classificação , Marburgvirus/imunologia , Marburgvirus/patogenicidade , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Vacinas Virais/imunologiaRESUMO
Cleavage of the glycoproteins of many virus species by furin and other host cell proteases is required for virus infectivity and, hence, determines viral pathogenicity. Proteolytic processing of Marburg virus and Ebola virus glycoproteins is also mediated by furin; however, for Ebola virus, in contrast to other viruses, glycoprotein cleavage is dispensable for replication in vitro, as has been shown in previous studies. In the present study, by use of a highly potent and selective furin inhibitor, we demonstrate that glycoprotein cleavage inhibition results in a minimal reduction in the virus titer that is insufficient to block filoviral replication. Thus, furin inhibitors are unlikely to be effective in the treatment of filoviral infections.
Assuntos
Antivirais/farmacologia , Filoviridae/fisiologia , Glicoproteínas/fisiologia , Proteínas Virais/fisiologia , Animais , Anticorpos Monoclonais/imunologia , Chlorocebus aethiops , Filoviridae/classificação , Filoviridae/efeitos dos fármacos , Glicoproteínas/antagonistas & inibidores , Glicoproteínas/imunologia , Haplorrinos , Humanos , Immunoblotting , Rim , Marburgvirus/classificação , Marburgvirus/efeitos dos fármacos , Marburgvirus/fisiologia , Camundongos , Peptídeo Hidrolases/metabolismo , Sorotipagem , Células Vero , Proteínas Virais/antagonistas & inibidoresRESUMO
The complete genome sequences of 2 closely related plaque-derived variants of Marburg virus (MARV) species Lake Victoria marburgvirus, strain Musoke, indicate only a few regions of the RNA genome as underlying the differences between the 2 viruses. One variant is >90% lethal for guinea pigs and the other much less virulent, when guinea pigs are challenged with 1000 pfu of virus. Only 4 mutations that result in amino acid changes were identified, 1 in viral matrix protein VP40 and 3 in L, the RNA-dependent RNA polymerase. In addition, 6 differences were identified in noncoding regions of transcribed mRNA, and 1 silent codon change was identified in the L gene. Interestingly, the amino acid mutation identified in VP40 occurs in a nonconserved loop structure between 2 domains that are homologues only among MARV species. The L gene mutations were equally intriguing, clustering near a highly conserved motif in viral RNA-dependent RNA polymerases.
Assuntos
Variação Genética , Doença do Vírus de Marburg/mortalidade , Doença do Vírus de Marburg/fisiopatologia , Marburgvirus/genética , Animais , DNA Complementar/genética , DNA Viral/genética , Modelos Animais de Doenças , Cobaias , Marburgvirus/classificação , Marburgvirus/patogenicidade , RNA Viral/genética , RNA Viral/isolamento & purificação , Especificidade da Espécie , Ensaio de Placa ViralRESUMO
Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80-90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus.
Assuntos
Quirópteros/virologia , Doença do Vírus de Marburg/diagnóstico , Marburgvirus/genética , África/epidemiologia , Animais , Animais Selvagens/virologia , Sequência de Bases , Reservatórios de Doenças , Feminino , Humanos , Masculino , Doença do Vírus de Marburg/epidemiologia , Marburgvirus/classificação , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , ZoonosesRESUMO
Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients. MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV) expressing the glycoprotein of the Musoke strain of MARV (VSVDeltaG/MARVGP-Musoke). We used this vaccine to demonstrate complete protection of cynomolgus monkeys against a homologous MARV challenge. While these results are highly encouraging, an effective vaccine would need to confer protection against all relevant strains of MARV. Here, we evaluated the protective efficacy of the VSVDeltaG/MARVGP-Musoke vaccine against two heterologous MARV strains, the seemingly more pathogenic Angola strain and the more distantly related Ravn strain. In this study, seven cynomolgus monkeys were vaccinated with the VSVDeltaG/MARVGP-Musoke vector. Three of these animals were challenged with the Angola strain, three with the Ravn strain, and a single animal with the Musoke strain of MARV. Two animals served as controls and were each injected with a nonspecific VSV vector; these controls were challenged with the Angola and Ravn strains, respectively. Both controls succumbed to challenge by day 8. However, none of the specifically vaccinated animals showed any evidence of illness either from the vaccination or from the MARV challenges and all of these animals survived. These data suggest that the VSVDeltaG/MARVGP-Musoke vaccine should be sufficient to protect against all known MARV strains.
Assuntos
Doença do Vírus de Marburg/imunologia , Marburgvirus/classificação , Marburgvirus/imunologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos/imunologia , Reações Cruzadas/imunologia , Macaca fascicularis , Doença do Vírus de Marburg/genética , Doença do Vírus de Marburg/metabolismo , Marburgvirus/genética , Marburgvirus/metabolismo , Filogenia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Proteínas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/metabolismo , Viremia/sangue , Viremia/imunologia , Viremia/virologiaRESUMO
Ebola and Marburg viruses, family Filoviridae, are among the best known examples of emerging and re-emerging pathogens. Although outbreaks have been sporadic and geographically restricted to areas of Central Africa, the hemorrhagic fevers caused by these viruses are remarkably severe and are associated with high case fatality rates often exceeding 80 percent. In addition to humans, these viruses have decimated populations of wild apes in Central Africa. Currently, there are no vaccines or effective therapies available for human use. Progress in understanding the geneses of the pathophysiological changes that make filoviral infections of humans so destructive has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the molecular mechanisms of filoviral pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. In addition, substantial progress has been made in developing recombinant vaccines against these viruses.