A5064600641- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Hepatitis B Virus Studies
- Disaster Response and Management
- Vector-Borne Animal Diseases
- COVID-19 epidemiological studies
- Bacillus and Francisella bacterial research
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Virology and Viral Diseases
- Respiratory viral infections research
- CRISPR and Genetic Engineering
- Zoonotic diseases and public health
- Animal Virus Infections Studies
- Vaccine Coverage and Hesitancy
- Plant and animal studies
- Insect and Arachnid Ecology and Behavior
- bioluminescence and chemiluminescence research
- interferon and immune responses
- Transgenic Plants and Applications
- RNA Interference and Gene Delivery
- Animal Disease Management and Epidemiology
Friedrich-Loeffler-Institut
2015-2024
National Institute of Allergy and Infectious Diseases
2011-2023
National Institutes of Health
2011-2023
Institute of Molecular Biology
2023
United States Naval Medical Research Unit SOUTH
2017
Centers for Disease Control and Prevention
2015-2017
The University of Texas Medical Branch at Galveston
2017
Mayo Clinic
2017
The University of Texas at El Paso
2017
Philipps University of Marburg
2010-2016
Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers preformed nucleocapsids, but their biological significance has been debated, and they have suggested to be aggregates viral proteins without any further function. However, recent data for other viruses that produce similar structures inclusion might involved genome replication transcription. In order study filovirus bodies, we fused mCherry the polymerase L, which is found bodies. The...
Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at field diagnostic laboratory Liberia the current Ebola virus outbreak.
ABSTRACT Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- replication-competent virus-like particle (trVLP) allow of the virus life under BSL2 conditions; however, all current model only certain aspects cycle, rely on plasmid-based viral protein expression, have been used single cycles. We developed novel system...
Marburg virus belongs to the genus Marburgvirus in family Filoviridae and causes a severe hemorrhagic fever, known as fever (MHF), both humans nonhuman primates. Similar more widely Ebola MHF is characterized by systemic viral replication, immunosuppression abnormal inflammatory responses. These pathological features of disease contribute number dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure shock, often resulting death. A detailed...
The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that this outbreak EBOV mutating twice as fast previously observed, which indicates the potential for changes transmissibility and virulence could render current molecular diagnostics countermeasures ineffective. We have determined additional full-length sequences from two clusters imported infections into Mali, we show nucleotide substitution rate (9.6 × 10(-4) substitutions per...
For Ebola virus (EBOV), 4 different species are known: Zaire, Sudan, Côte d'Ivoire, and Reston ebolavirus. The newly discovered Bundibugyo ebolavirus has been proposed as a 5th species. So far, no cross-neutralization among EBOV described, aggravating progress toward cross-species protective vaccines. With the use of recombinant vesicular stomatitis (rVSV)-based vaccines, guinea pigs could be protected against Zaire (ZEBOV) infection only when immunized with vector expressing homologous, but...
Infectious virus-like particle (iVLP) systems have recently been established for several negative-strand RNA viruses, including the highly pathogenic Zaire ebolavirus (ZEBOV), and allow study of viral life cycle under biosafety level 2 conditions. However, current depend on expression helper nucleocapsid proteins in target cells, thus making it impossible to determine whether ribonucleoprotein complexes transferred by iVLPs are able facilitate initial transcription, an indispensable step...
The morphogenesis and budding of virus particles represent an important stage in the life cycle viruses. For Ebola virus, this process is driven by its major matrix protein, VP40. Like proteins many other nonsegmented, negative-strand RNA viruses, VP40 has been demonstrated to oligomerize occur at least two distinct oligomeric states: hexamers octamers, which are composed antiparallel dimers. While it shown that oligomers essential for viral cycle, their function completely unknown. Here we...
Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While molecular basis for this difference remains unclear, vitro evidence suggested a role glycoprotein (GP) as major filovirus pathogenicity factor, but direct such context of virus infection notably lacking. In order to assess GP EBOV virulence, we have developed novel reverse genetics system...
Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5′ and 3′ untranslated regions (UTRs) present the seven viral transcriptional units. To date, specific functions have not been assigned these UTRs. With reporter assays, we demonstrated that Zaire ebolavirus (EBOV) 5′-UTRs lack internal ribosomal entry site function. However, do differentially regulate cap-dependent translation when placed...
Ebola virus causes devastating hemorrhagic fever outbreaks for which no approved therapeutic exists. The viral nucleocapsid, is minimally composed of the proteins NP, VP35, and VP24, represents an attractive target drug development; however, molecular determinants that govern interactions functions these three are still unknown. Through a series mutational analyses, in combination with biochemical bioinformatics approaches, we identified region on VP24 was critical its interaction NP....
The 2014–2016 Ebola virus (EBOV) outbreak in West Africa highlighted the need for improved therapeutic options against this virus. Approaches targeting host factors/pathways essential are advantageous because they can potentially target a wide range of viruses, including newly emerging ones and development resistance is less likely than when directly. However, systematic approaches screening factors important EBOV have been hampered by necessity to work with at biosafety level 4 (BSL4). In...
The ongoing Ebola outbreak in West Africa has resulted 28 646 suspected, probable, and confirmed virus infections. Nevertheless, malaria remains a large public health burden the region affected by outbreak. A joint Centers for Disease Control Prevention/National Institutes of Health diagnostic laboratory was established Monrovia, Liberia, August 2014, to provide diagnostics virus.All blood samples from suspected virus-infected patients admitted Médecins Sans Frontières ELWA3 treatment unit...
In general, Ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. However, despite substantial sequence homology other members of the family Filoviridae, Reston ebolavirus displays reduced pathogenicity primates has never been demonstrated clinical disease humans, its infection. order develop a tool explore potential roles transcription replication ebolavirus, we developed an RNA polymerase I (Pol I)-driven minigenome system....
To facilitate an understanding of the molecular aspects pathogenesis Zaire ebolavirus (ZEBOV) infection, we generated 2 different recombinant viruses expressing enhanced green fluorescent protein (eGFP) from additional transcription units inserted at positions in virus genome. These showed vitro phenotypes similar to that wild-type ZEBOV (wt-ZEBOV) and were stable over multiple passages. Infection with one eGFP produced only mild disease rhesus macaques, demonstrating a marked attenuation...
The Z protein has been shown for several arenaviruses to serve as the viral matrix protein. As such, provides principal force budding of virus particles and is capable forming virus-like (VLPs) when expressed alone. For most arenaviruses, this activity be linked presence proline-rich late-domain motifs in C terminus; however, New World arenavirus Tacaribe (TCRV), no such motif exists within Z. It was recently demonstrated that while TCRV still functioning a induce formation VLPs, neither its...