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Vector Borne and Zoonotic Diseases... Sep 2022Outbreaks of African filoviruses often have high mortality, including more than 11,000 deaths among 28,562 cases during the West Africa Ebola outbreak of 2014-2016.... (Review)
Review
Outbreaks of African filoviruses often have high mortality, including more than 11,000 deaths among 28,562 cases during the West Africa Ebola outbreak of 2014-2016. Numerous studies have investigated the factors that contributed to individual filovirus outbreaks, but there has been little quantitative synthesis of this work. In addition, the ways in which the typical causes of filovirus outbreaks differ from other zoonoses remain poorly described. In this study, we quantify factors associated with 45 outbreaks of African filoviruses (ebolaviruses and Marburg virus) using a rubric of 48 candidate causal drivers. For filovirus outbreaks, we reviewed >700 peer-reviewed and gray literature sources and developed a list of the factors reported to contribute to each outbreak (, a "driver profile" for each outbreak). We compare and contrast the profiles of filovirus outbreaks to 200 background outbreaks, randomly selected from a global database of 4463 outbreaks of bacterial and viral zoonotic diseases. We also test whether the quantitative patterns that we observed were robust to the influences of six covariates, country-level factors such as gross domestic product, population density, and latitude that have been shown to bias global outbreak data. We find that, regardless of whether covariates are included or excluded from models, the driver profile of filovirus outbreaks differs from that of background outbreaks. Socioeconomic factors such as trade and travel, wild game consumption, failures of medical procedures, and deficiencies in human health infrastructure were more frequently reported in filovirus outbreaks than in the comparison group. Based on our results, we also present a review of drivers reported in at least 10% of filovirus outbreaks, with examples of each provided.
Topics: Animals; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Marburg Virus Disease; Marburgvirus
PubMed: 36084314
DOI: 10.1089/vbz.2022.0020 -
Viruses Sep 2015The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola... (Review)
Review
The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in comparison, the seven other known filovirus family members are significantly understudied. Many of these, including Marburgviruses and Ebolaviruses other than EBOV, are also highly virulent and fully capable of causing widespread epidemics. This review places the focus on these non-EBOV filoviruses, including known immunological and pathological data. The available animal models, research tools and currently available therapeutics will also be discussed along with an emphasis in the large number of current gaps in knowledge of these less highlighted filoviruses. It is evident that much research is yet to be done in order to bring the non-EBOV filovirus field to the forefront of current research and, importantly, to the development of more effective vaccines and therapeutics to combat potential future outbreaks.
Topics: Animals; Biomedical Research; Disease Models, Animal; Disease Outbreaks; Filoviridae; Filoviridae Infections; Humans; Virulence
PubMed: 26426036
DOI: 10.3390/v7102867 -
Scientific Reports Jul 2023Lloviu cuevavirus (LLOV) was the first identified member of Filoviridae family outside the Ebola and Marburgvirus genera. A massive die-off of Schreibers's bats...
Lloviu cuevavirus (LLOV) was the first identified member of Filoviridae family outside the Ebola and Marburgvirus genera. A massive die-off of Schreibers's bats (Miniopterus schreibersii) in the Iberian Peninsula in 2002 led to its initial discovery. Recent studies with recombinant and wild-type LLOV isolates confirmed the zoonotic nature of the virus in vitro. We examined bat samples from Italy for the presence of LLOV in an area outside of the currently known distribution range of the virus. We detected one positive sample from 2020, sequenced the complete coding region of the viral genome and established an infectious isolate of the virus. In addition, we performed the first comprehensive evolutionary analysis of the virus, using the Spanish, Hungarian and the Italian sequences. The most important achievement of this study is the establishment of an additional infectious LLOV isolate from a bat sample using the SuBK12-08 cells, demonstrating that this cell line is highly susceptible to LLOV infection and confirming the previous observation that these bats are effective hosts of the virus in nature. This result further strengthens the role of bats as the natural hosts for zoonotic filoviruses.
Topics: Animals; Chiroptera; Filoviridae; Marburgvirus; Cell Line; Italy; Phylogeny
PubMed: 37443182
DOI: 10.1038/s41598-023-38364-7 -
Microbial Physiology 2020For decades it has been known that infectious agents including pathogenic protozoans, bacteria, and viruses, adapted to a particular animal host, can mutate to gain the... (Review)
Review
For decades it has been known that infectious agents including pathogenic protozoans, bacteria, and viruses, adapted to a particular animal host, can mutate to gain the ability to infect another host, and the mechanisms involved have been studied in great detail. Although an infectious agent in one animal can alter its host range with relative ease, no example of a plant virus changing its host organism to an animal has been documented. One prevalent pathway for the transmission of infectious agents between hosts involves ingestion of the flesh of one organism by another. In this article we document numerous examples of viral and prion diseases transmitted by eating animals. We suggest that the occurrence of cross-species viral epidemics can be substantially reduced by shifting to a more vegetarian diet and enforcing stricter laws that ban the slaughter and trade of wild and endangered species.
Topics: Animals; Birds; COVID-19; Coronavirus; Diet Therapy; Eating; Ebolavirus; Epidemics; HIV; Host Specificity; Humans; Influenza in Birds; Marburgvirus; Orthomyxoviridae; Plant Viruses; Prion Diseases; SARS-CoV-2; Viral Zoonoses; Virus Diseases
PubMed: 32957108
DOI: 10.1159/000511192 -
PLoS Pathogens Aug 2023Ebola (EBOV) and Marburg viruses (MARV) cause severe hemorrhagic fever associated with high mortality rates in humans. A better understanding of filovirus-host...
Ebola (EBOV) and Marburg viruses (MARV) cause severe hemorrhagic fever associated with high mortality rates in humans. A better understanding of filovirus-host interactions that regulate the EBOV and MARV lifecycles can provide biological and mechanistic insight critical for therapeutic development. EBOV glycoprotein (eGP) and MARV glycoprotein (mGP) mediate entry into host cells primarily by actin-dependent macropinocytosis. Here, we identified actin-binding cytoskeletal crosslinking proteins filamin A (FLNa) and B (FLNb) as important regulators of both EBOV and MARV entry. We found that entry of pseudotype psVSV-RFP-eGP, infectious recombinant rVSV-eGP-mCherry, and live authentic EBOV and MARV was inhibited in filamin A knockdown (FLNaKD) cells, but was surprisingly enhanced in filamin B knockdown (FLNbKD) cells. Mechanistically, our findings suggest that differential regulation of macropinocytosis by FLNa and FLNb likely contributes to their specific effects on EBOV and MARV entry. This study is the first to identify the filamin family of proteins as regulators of EBOV and MARV entry. These findings may provide insight into the development of new countermeasures to prevent EBOV and MARV infections.
Topics: Humans; Filamins; Ebolavirus; Actins; Hemorrhagic Fever, Ebola; Marburgvirus; Glycoproteins
PubMed: 37585478
DOI: 10.1371/journal.ppat.1011595 -
Journal of Molecular Biology Oct 2019Research on filoviruses has historically focused on the highly pathogenic ebola- and marburgviruses. Indeed, until recently, these were the only two genera in the... (Review)
Review
Research on filoviruses has historically focused on the highly pathogenic ebola- and marburgviruses. Indeed, until recently, these were the only two genera in the filovirus family. Recent advances in sequencing technologies have facilitated the discovery of not only a new ebolavirus, but also three new filovirus genera and a sixth proposed genus. While two of these new genera are similar to the ebola- and marburgviruses, the other two, discovered in saltwater fishes, are considerably more diverse. Nonetheless, these viruses retain a number of key features of the other filoviruses. Here, we review the key characteristics of filovirus replication and transcription, highlighting similarities and differences between the viruses. In particular, we focus on key regulatory elements in the genomes, replication and transcription strategies, and the conservation of protein domains and functions among the viruses. In addition, using computational analyses, we were able to identify potential homology and functions for some of the genes of the novel filoviruses with previously unknown functions. Although none of the newly discovered filoviruses have yet been isolated, initial studies of some of these viruses using minigenome systems have yielded insights into their mechanisms of replication and transcription. In general, the Cuevavirus and proposed Dianlovirus genera appear to follow the transcription and replication strategies employed by the ebola- and marburgviruses, respectively. While our knowledge of the fish filoviruses is currently limited to sequence analysis, the lack of certain conserved motifs and even entire genes necessitates that they have evolved distinct mechanisms of replication and transcription.
Topics: Filoviridae; Genome, Viral; Regulatory Elements, Transcriptional; Virus Replication
PubMed: 31260690
DOI: 10.1016/j.jmb.2019.06.029 -
Microbiology and Molecular Biology... May 2020In 1967, several workers involved in poliomyelitis vaccine development and production fell ill at three different locations in Europe with a severe and often lethal... (Review)
Review
In 1967, several workers involved in poliomyelitis vaccine development and production fell ill at three different locations in Europe with a severe and often lethal novel disease associated with grivets () imported from Uganda. This disease was named Marburg virus disease (MVD) after the West German town of Marburg an der Lahn, where most human infections and deaths had been recorded. Consequently, the Marburg episode received the most scientific and media attention. Cases that occurred in Frankfurt am Main, West Germany, were also described in commonly accessible scientific literature, although they were less frequently cited than those pertaining to the Marburg infections. However, two infections occurring in a third location, in Belgrade, Yugoslavia, have seemingly been all but forgotten. Due in part to their absence in commonly used databases and in part to the fact that they were written in languages other than English, the important articles describing this part of the outbreak are very rarely cited. Here, we summarize this literature and correct published inaccuracies to remind a younger generation of scientists focusing on Marburg virus and its closest filoviral relatives of this important historical context. Importantly, and unfortunately, the three episodes of infection of 1967 still represent the best in-depth clinical look at MVD in general and in the context of "modern" medicine (fully resourced versus less-resourced capacity) in particular. Hence, each individual case of these episodes holds crucial information for health care providers who may be confronted with MVD today.
Topics: Animals; Chlorocebus aethiops; Disease Outbreaks; History, 20th Century; Humans; Laboratory Infection; Marburg Virus Disease; Marburgvirus; Uganda; Yugoslavia
PubMed: 32404328
DOI: 10.1128/MMBR.00095-19 -
Virology Journal Dec 2019Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often... (Review)
Review
Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often characterized by a lack of resources and facilities to diagnose and treat patients. There are currently no approved vaccines or treatments, and the chaotic and infrequent nature of outbreaks, among other factors, makes testing new countermeasures during outbreaks ethically and logistically challenging. Without field efficacy studies, researchers must rely on animal models of MARV infection to assess the efficacy of vaccines and treatments, with the limitations being the accuracy of the animal model in recapitulating human pathogenesis. This review will compare various animal models to the available descriptions of human pathogenesis and aims to evaluate their effectiveness in modeling important aspects of Marburg virus disease.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Marburg Virus Disease; Marburgvirus
PubMed: 31888676
DOI: 10.1186/s12985-019-1272-z -
Viruses Sep 2012The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF) in humans and nonhuman primates. Because many cases have occurred in geographical areas... (Review)
Review
The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF) in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (NHPs), guinea pigs and mice as animal models. NHPs appear to closely mirror filoviral HF in humans (based on limited clinical data), but only small numbers may be used in carefully regulated experiments; much research is therefore done in rodents. Because of their availability in large numbers and the existence of a wealth of reagents for biochemical and immunological testing, mice have become the preferred small animal model for filovirus research. Since the first experiments following the initial 1967 marburgvirus outbreak, wild-type or mouse-adapted viruses have been tested in immunocompetent or immunodeficient mice. In this paper, we review how these types of studies have been used to investigate the pathogenesis of filoviral disease, identify immune responses to infection and evaluate antiviral drugs and vaccines. We also discuss the strengths and weaknesses of murine models for filovirus research, and identify important questions for further study.
Topics: Animals; Disease Models, Animal; Ebolavirus; Hemorrhagic Fever, Ebola; Marburg Virus Disease; Marburgvirus; Mice
PubMed: 23170168
DOI: 10.3390/v4091477 -
The Journal of Infectious Diseases Nov 2023Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as...
Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as a promising strategy for the treatment of filovirus disease. Here, we describe 2 distinct cross-reactive monoclonal antibodies (mAbs) isolated from mice immunized with recombinant vesicular stomatitis virus-based filovirus vaccines. Both mAbs recognized the glycoproteins of multiple different ebolaviruses and exhibited broad but differential in vitro neutralization activities against these viruses. By themselves, each mAb provided partial to full protection against Ebola virus in mice, and in combination, the mAbs provided 100% protection against Sudan virus challenge in guinea pigs. This study identified novel mAbs that were elicited through immunization and able to provide protection from ebolavirus infection, thus enriching the pool of candidate therapeutics for treating Ebola disease.
Topics: Humans; Animals; Guinea Pigs; Mice; Hemorrhagic Fever, Ebola; Ebolavirus; Antibodies, Monoclonal; Combined Antibody Therapeutics; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37288609
DOI: 10.1093/infdis/jiad205