The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Heinz Feldmann - One of the best experts on this subject based on the ideXlab platform.
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recombinant vesicular stomatitis Virus based vaccines against ebola and Marburg Virus infections
The Journal of Infectious Diseases, 2011Co-Authors: Thomas W Geisbert, Heinz FeldmannAbstract:The filoViruses, Marburg Virus and Ebola Virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filoVirus vaccines under development is a system based on recombinant vesicular stomatitis Virus (rVSV) that expresses a single filoVirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filoVirus vaccines was shown to completely protect nonhuman primates against Marburg Virus and 3 different species of Ebola Virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filoVirus infections, and a rVSV-based Ebola Virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg Virus infections.
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Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections
The Journal of Infectious Diseases, 2011Co-Authors: Thomas W Geisbert, Heinz FeldmannAbstract:The filoViruses, Marburg Virus and Ebola Virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filoVirus vaccines under development is a system based on recombinant vesicular stomatitis Virus (rVSV) that expresses a single filoVirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filoVirus vaccines was shown to completely protect nonhuman primates against Marburg Virus and 3 different species of Ebola Virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filoVirus infections, and a rVSV-based Ebola Virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg Virus infections.
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antibody dependent enhancement of Marburg Virus infection
The Journal of Infectious Diseases, 2011Co-Authors: Eri Nakayama, Heinz Feldmann, Daisuke Tomabechi, Keita Matsuno, Noriko Kishida, Reiko Yoshida, Ayato TakadaAbstract:Background. Marburg Virus (MARV) and Ebola Virus (EBOV) cause severe hemorrhagic fever in primates. Earlier studies demonstrated that antibodies to particular epitopes on the glycoprotein (GP) of EBOV enhanced Virus infectivity in vitro. Methods. To investigate this antibody-dependent enhancement (ADE) in MARV infection, we produced mouse antisera and monoclonal antibodies (mAbs) to the GPs of MARV strains Angola and Musoke. Results. The infectivity of vesicular stomatitis Virus pseudotyped with Angola GP in K562 cells was significantly enhanced in the presence of Angola GP antisera, whereas only minimal ADE activity was seen with Musoke GP antisera. This difference correlated with the percentage of hybridoma clones producing infectivity-enhancing mAbs. Using mAbs to MARV GP, we identified 3 distinct ADE epitopes in the mucinlike region on Angola GP. Interestingly, some of these antibodies bound to both Angola and Musoke GPs but showed significantly higher ADE activity for strain Angola. ADE activity depended on epitopes in the mucinlike region and glycine at amino acid position 547, present in the Angola but absent in the Musoke GP. Conclusions. These results suggest a possible link between ADE and MARV pathogenicity and provide new insights into the mechanisms underlying ADE entry of filoViruses.
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postexposure treatment of Marburg Virus infection
Emerging Infectious Diseases, 2010Co-Authors: Thomas W Geisbert, Lisa Hensley, Joan B Geisbert, Anders Leung, Joshua C Johnson, Allen Grolla, Heinz FeldmannAbstract:Rhesus monkeys are protected from disease when a recombinant vesicular stomatitis Virus–based vaccine is administered 20–30 min after infection with Marburg Virus. We protected 5/6 monkeys when this vaccine was given 24 h after challenge; 2/6 animals were protected when the vaccine was administered 48 h postinfection.
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Proteolytic processing of Marburg Virus glycoprotein.
Virology, 2000Co-Authors: Viktor E. Volchkov, Ute Ströher, Stephan Becker, Hansdieter Klenk, Valentina A. Volchkova, Olga Dolnik, Michael Cieplik, Wolfgang Garten, Heinz FeldmannAbstract:Abstract Processing of the transmembrane glycoprotein (GP) of Marburg Virus involved the conversion of an endo H-sensitive, ER-specific form into an endo H-resistant, Golgi-specific precursor that was cleaved into GP 1 and GP 2 . Cleavage was mediated by furin or another subtilisin-like endoprotease with similar substrate specificity as indicated by mutational analysis of the cleavage site and inhibition using peptidyl chloromethylketones. Mature GP consisted of disulfide-linked GP 1 and GP 2 subunits.
Thomas W Geisbert - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections
The Journal of Infectious Diseases, 2011Co-Authors: Thomas W Geisbert, Heinz FeldmannAbstract:The filoViruses, Marburg Virus and Ebola Virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filoVirus vaccines under development is a system based on recombinant vesicular stomatitis Virus (rVSV) that expresses a single filoVirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filoVirus vaccines was shown to completely protect nonhuman primates against Marburg Virus and 3 different species of Ebola Virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filoVirus infections, and a rVSV-based Ebola Virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg Virus infections.
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recombinant vesicular stomatitis Virus based vaccines against ebola and Marburg Virus infections
The Journal of Infectious Diseases, 2011Co-Authors: Thomas W Geisbert, Heinz FeldmannAbstract:The filoViruses, Marburg Virus and Ebola Virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filoVirus vaccines under development is a system based on recombinant vesicular stomatitis Virus (rVSV) that expresses a single filoVirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filoVirus vaccines was shown to completely protect nonhuman primates against Marburg Virus and 3 different species of Ebola Virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filoVirus infections, and a rVSV-based Ebola Virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg Virus infections.
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postexposure treatment of Marburg Virus infection
Emerging Infectious Diseases, 2010Co-Authors: Thomas W Geisbert, Lisa Hensley, Joan B Geisbert, Anders Leung, Joshua C Johnson, Allen Grolla, Heinz FeldmannAbstract:Rhesus monkeys are protected from disease when a recombinant vesicular stomatitis Virus–based vaccine is administered 20–30 min after infection with Marburg Virus. We protected 5/6 monkeys when this vaccine was given 24 h after challenge; 2/6 animals were protected when the vaccine was administered 48 h postinfection.
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characterization of a new Marburg Virus isolated from a 1987 fatal case in kenya
Archives of virology. Supplementum, 1996Co-Authors: E D Johnson, B.k. Johnson, Thomas W Geisbert, D Silverstein, P Tukei, Aranzazu Sanchez, Peter B JahrlingAbstract:In 1987, an isolated case of fatal Marburg disease was recognized during routine clinical haemorrhagic fever Virus surveillance conducted in Kenya. This report describes the isolation and partial characterization of the new Marburg Virus (strain Ravn) isolated from this case. The Ravn isolate was indistinguishable from reference Marburg Virus strains by cross-neutralization testing. Virus particles and aggregates of Marburg nucleocapsid matrix in Ravn-infected vero cells, were visualized by immunoelectron microscopic techniques, and also in tissues obtained from the patient and from inoculated monkeys. The cell culture isolate produced a haemorrhagic disease typical of Marburg Virus infection when inoculated into rhesus monkeys. Disease was characterized by the sudden appearance of fever and anorexia within 4 to 7 days, and death by day 11. Comparison of nucleotide sequences for portions of the glycoprotein genes of Marburg-Ravn were compared with Marburg reference strains Musoki (MUS) and Popp (POP). Nucleotide identity in this alignment between RAV and MUS is 72.3%, RAV and POP is 71%, and MUS and POP is 91.7%. Amino acid identity between RAV and MUS is 72%, RAV and POP is 67%, and MUS and POP is 93%. These data suggest that Ravn is another subtype of Marburg Virus, analogous to the emerging picture of a spectrum of Ebola geographic isolates and subtypes.
Stephan Becker - One of the best experts on this subject based on the ideXlab platform.
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live cell imaging of Marburg Virus infected cells uncovers actin dependent transport of nucleocapsids over long distances
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Gordian Schudt, Larissa Kolesnikova, Olga Dolnik, Beate Sodeik, Stephan BeckerAbstract:Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola Viruses, related Viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg Virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg Virus from infected cells.
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The Cytoplasmic Domain of Marburg Virus GP Modulates Early Steps of Viral Infection
Journal of Virology, 2011Co-Authors: Evamaria Mittler, Larissa Kolesnikova, Bettina Hartlieb, Robert A. Davey, Stephan BeckerAbstract:Marburg Virus infection is mediated by the only viral surface protein, GP, a trimeric type I transmembrane protein. While its ectodomain mediates receptor binding and fusion of viral and cellular membranes and its transmembrane domain is essential for the recruitment of GP into budding particles by the matrix protein VP40, the role of the short cytoplasmic domain has remained enigmatic. Here we show that a missing cytoplasmic domain did not impair trimerization, intracellular transport, or incorporation of GP into infectious Marburg Virus-like particles (iVLPs) but altered the glycosylation pattern as well as the recognition of GP by neutralizing antibodies. These results suggest that subtle conformational changes took place in the ectodomain. To investigate the function of the cytoplasmic domain during viral entry, a novel entry assay was established to monitor the uptake of filamentous VLPs by measuring the occurrence of luciferase-labeled viral nucleocapsids in the cytosol of target cells. This quantitative assay showed that the entry process of VLPs incorporating GP missing its cytoplasmic domain (GPΔCD) was impaired. Supporting these results, iVLPs incorporating a mutant GP missing its cytoplasmic domain were significantly less infectious than iVLPs containing wild-type GP. Taken together, the data indicate that the absence of the short cytoplasmic domain of Marburg Virus GP may induce conformational changes in the ectodomain which impact the filoviral entry process.
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vacuolar protein sorting pathway contributes to the release of Marburg Virus
Journal of Virology, 2009Co-Authors: Larissa Kolesnikova, Stephan Becker, Thomas Strecker, Eiji Morita, Florian Zielecki, Evamaria Mittler, Colin M CrumpAbstract:VP40, the major matrix protein of Marburg Virus, is the main driving force for viral budding. Additionally, cellular factors are likely to play an important role in the release of progeny Virus. In the present study, we characterized the influence of the vacuolar protein sorting (VPS) pathway on the release of Virus-like particles (VLPs), which are induced by Marburg Virus VP40. In the supernatants of HEK 293 cells expressing VP40, different populations of VLPs with either a vesicular or a filamentous morphology were detected. While the filaments were almost completely composed of VP40, the vesicular particles additionally contained considerable amounts of cellular proteins. In contrast to that in the vesicles, the VP40 in the filaments was regularly organized, probably inducing the elimination of cellular proteins from the released VLPs. Vesicular particles were observed in the supernatants of cells even in the absence of VP40. Mutation of the late-domain motif in VP40 resulted in reduced release of filamentous particles, and likewise, inhibition of the VPS pathway by expression of a dominant-negative (DN) form of VPS4 inhibited the release of filamentous particles. In contrast, the release of vesicular particles did not respond significantly to the expression of DN VPS4. Like the budding of VLPs, the budding of Marburg Virus particles was partially inhibited by the expression of DN VPS4. While the release of VLPs from VP40-expressing cells is a valuable tool with which to investigate the budding of Marburg Virus particles, it is important to separate filamentous VLPs from vesicular particles, which contain many cellular proteins and use a different budding mechanism.
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Morphology of Marburg Virus NP–RNA
Virology, 2002Co-Authors: Manos Mavrakis, Larissa Kolesnikova, Guy Schoehn, Stephan Becker, Rob W. H. RuigrokAbstract:Abstract When Marburg Virus (MBGV) nucleoprotein (NP) is expressed in insect cells, it binds to cellular RNA and forms NP–RNA complexes such as insect cell-expressed nucleoproteins from other nonsegmented negative-strand RNA Viruses. Recombinant MBGV NP–RNA forms loose coils that resemble rabies Virus N–RNA. MBGV NP monomers are rods that are spaced along the coil similar to the nucleoprotein monomers of the rabies Virus N–RNA. High salt treatment induces tight coiling of the MBGV NP–RNA, again a characteristic observed for other nonsegmented negative-strand Virus N–RNAs. Electron microscopy of fixed Marburg Virus particles shows that the viral nucleocapsid has a smaller diameter than the free, recombinant NP–RNA. This difference in helical parameters could be caused by the interaction of other viral proteins with the NP–RNA. A similar but opposite phenomenon is observed for rhabdoVirus nucleocapsids that are condensed by the viral matrix protein upon which they acquire a larger diameter. Finally, there appears to be an extensive and regular protein scaffold between the viral nucleocapsid and the membrane that seems not to exist in the other negative-strand RNA Viruses.
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Sorting of Marburg Virus Surface Protein and Virus Release Take Place at Opposite Surfaces of Infected Polarized Epithelial Cells
Journal of Virology, 2001Co-Authors: Christian Sänger, Elke Muhlberger, Larissa Kolesnikova, Elena I. Ryabchikova, Hansdieter Klenk, Stephan BeckerAbstract:Marburg Virus, a filoVirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of Marburg Virus in polarized epithelial cells. To this end, we established an MDCKII cell line that was able to express GP permanently (MDCK-GP). The functional integrity of GP expressed in these cells was analyzed using vesicular stomatitis Virus pseudotypes. Further experiments revealed that GP is transported in MDCK-GP cells mainly to the apical membrane and is released exclusively into the culture medium facing the apical membrane. When MDCKII cells were infected with Marburg Virus, the majority of GP was also transported to the apical membrane, suggesting that the protein contains an autonomous apical transport signal. Release of infectious progeny virions, however, took place exclusively at the basolateral membrane of the cells. Thus, vectorial budding of Marburg Virus is presumably determined by factors other than the surface protein.
Lisa Hensley - One of the best experts on this subject based on the ideXlab platform.
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new insights into Marburg Virus disease pathogenesis in the rhesus macaque model
The Journal of Infectious Diseases, 2018Co-Authors: Timothy K Cooper, Joshua C Johnson, Peter B Jahrling, Jennifer Sword, Amanda Bonilla, Randy Hart, John G Bernbaum, Kurt Cooper, Lisa HensleyAbstract:Previously, several studies have been performed to delineate the development and progression of Marburg Virus infection in nonhuman primates (NHPs), primarily to clarify the mechanisms of severe (fatal) disease. After the 2013-2016 Ebola Virus disease (EVD) epidemic in Western Africa, there has been a reassessment of the available filoVirus animal models and the utility of these to faithfully recapitulate human disease. The high lethality of the NHP models has raised doubts as to their ability to provide meaningful data for the full spectrum of disease observed in humans. Of particular interest are the etiologic and pathophysiologic mechanisms underlying postconvalescent sequelae observed in human survivors of EVD and Marburg Virus disease (MVD). In the current study, we evaluated the lesions of MVD in NHPs; however, in contrast to previous studies, we focused on the potential for development of sequelae similar to those reported in human survivors of MVD and EVD. We found that during acute MVD in the macaque model, there is frequent inflammation of peripheral nerves, autonomic ganglia, and the iris of the eye. Furthermore, we demonstrate viral infection of the ocular ciliary body and retina, testis, epididymis, ovary, oviduct, uterine endometrium, prostate, and mammary gland. These findings are relevant for both development of postconvalescent sequelae and the natural transmission of Virus.
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Transcriptional Profiling of the Immune Response to Marburg Virus Infection
Journal of Virology, 2015Co-Authors: Ignacio S. Caballero, Judy Yen, Sara Garamszegi, Shikha Malhotra, Arthur J. Goff, Lisa Hensley, John H. Connor, Kenny LinAbstract:Marburg Virus is a genetically simple RNA Virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg Virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg Virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg Virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg Virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg Virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg Virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the immune cells circulating in the blood of infected primates respond following exposure to Marburg Virus. Our results show that there are three discernible stages of response to infection that correlate with presymptomatic, early, and late symptomatic stages of infection, a response format similar to that seen following challenge with other hemorrhagic fever Viruses. In contrast to the ability of the Virus to block innate immune signaling in vitro , the earliest and most sustained response is an interferon-like response. Our analysis also identifies a number of cytokines that are transcriptionally upregulated during late stages of infection and suggest that there is a Th2-skewed response to infection. When correlated with companion data describing the animal model from which our samples were collected, our results suggest that the innate immune response may contribute to overall pathogenesis.
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postexposure treatment of Marburg Virus infection
Emerging Infectious Diseases, 2010Co-Authors: Thomas W Geisbert, Lisa Hensley, Joan B Geisbert, Anders Leung, Joshua C Johnson, Allen Grolla, Heinz FeldmannAbstract:Rhesus monkeys are protected from disease when a recombinant vesicular stomatitis Virus–based vaccine is administered 20–30 min after infection with Marburg Virus. We protected 5/6 monkeys when this vaccine was given 24 h after challenge; 2/6 animals were protected when the vaccine was administered 48 h postinfection.
Gary Wong - One of the best experts on this subject based on the ideXlab platform.
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post exposure immunotherapy for two ebolaViruses and Marburg Virus in nonhuman primates
Nature Communications, 2019Co-Authors: Jennifer M Brannan, Shihua He, Gary Wong, Sergey Shulenin, Katie A Howell, Laura I Prugar, Hong Vu, Shweta Kailasan, Henna RainaAbstract:The 2013–2016 Ebola Virus (EBOV) disease epidemic demonstrated the grave consequences of filoVirus epidemics in the absence of effective therapeutics. Besides EBOV, two additional ebolaViruses, Sudan (SUDV) and Bundibugyo (BDBV) Viruses, as well as multiple variants of Marburg Virus (MARV), have also caused high fatality epidemics. Current experimental EBOV monoclonal antibodies (mAbs) are ineffective against SUDV, BDBV, or MARV. Here, we report that a cocktail of two broadly neutralizing ebolaVirus mAbs, FVM04 and CA45, protects nonhuman primates (NHPs) against EBOV and SUDV infection when delivered four days post infection. This cocktail when supplemented by the anti-MARV mAb MR191 exhibited 100% efficacy in MARV-infected NHPs. These findings provide a solid foundation for clinical development of broadly protective immunotherapeutics for use in future filoVirus epidemics.
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Successful treatment of Marburg Virus with orally administrated T-705 (Favipiravir) in a mouse model.
Antiviral Research, 2018Co-Authors: Zirui Zhang, Shihua He, Gary Wong, Logan BanadygaAbstract:Abstract FiloViruses, such as Marburg and Ebola Viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of Viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg Virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg Virus (variant Angola). Moreover, lower doses of T-705 and higher doses administered later during infection (day 3 or 4 post-infection) showed partial efficacy, with at least half the infected mice surviving. Accordingly, we observed reductions in infectious Virus particles and Virus RNA levels following drug treatment that appeared to correlate with survival. Our findings suggest that T-705 may be an effective therapeutic against Marburg Virus and might be especially promising for use in the event of an outbreak, where it could be orally administered quickly and safely even after exposure.
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establishment and characterization of a lethal mouse model for the angola strain of Marburg Virus
Journal of Virology, 2014Co-Authors: Gary Wong, Jonathan Audet, Todd Cutts, Stephanie A Booth, Gary P KobingerAbstract:Infections with Marburg Virus (MARV) and Ebola Virus (EBOV) cause severe hemorrhagic fever in humans and nonhuman primates (NHPs) with fatality rates up to 90%. A number of experimental vaccine and treatment platforms have previously been shown to be protective against EBOV infection. However, the rate of development for prophylactics and therapeutics against MARV has been lower in comparison, possibly because a small-animal model is not widely available. Here we report the development of a mouse model for studying the pathogenesis of MARV Angola (MARV/Ang), the most virulent strain of MARV. Infection with the wild-type Virus does not cause disease in mice, but the adapted Virus (MARV/Ang-MA) recovered from liver homogenates after 24 serial passages in severe combined immunodeficient (SCID) mice caused severe disease when administered intranasally (i.n.) or intraperitoneally (i.p.). The median lethal dose (LD50) was determined to be 0.015 50% TCID50 (tissue culture infective dose) of MARV/Ang-MA in SCID mice, and i.p. infection at a dose of 1,000× LD50 resulted in death between 6 and 8 days postinfection in SCID mice. Similar results were obtained with immunocompetent BALB/c and C57BL/6 mice challenged i.p. with 2,000× LD50 of MARV/Ang-MA. Virological and pathological analyses of MARV/Ang-MA-infected BALB/c mice revealed that the associated pathology was reminiscent of observations made in NHPs with MARV/Ang. MARV/Ang-MA-infected mice showed most of the clinical hallmarks observed with Marburg hemorrhagic fever, including lymphopenia, thrombocytopenia, marked liver damage, and uncontrolled viremia. Virus titers reached 108 TCID50/ml in the blood and between 106 and 1010 TCID50/g tissue in the intestines, kidney, lungs, brain, spleen, and liver. This model provides an important tool to screen candidate vaccines and therapeutics against MARV infections. IMPORTANCE The Angola strain of Marburg Virus (MARV/Ang) was responsible for the largest outbreak ever documented for Marburg Viruses. With a 90% fatality rate, it is similar to Ebola Virus, which makes it one of the most lethal Viruses known to humans. There are currently no approved interventions for Marburg Virus, in part because a small-animal model that is vulnerable to MARV/Ang infection is not available to screen and test potential vaccines and therapeutics in a quick and economical manner. To address this need, we have adapted MARV/Ang so that it causes illness in mice resulting in death. The signs of disease in these mice are reminiscent of wild-type MARV/Ang infections in humans and nonhuman primates. We believe that this will be of help in accelerating the development of life-saving measures against Marburg Virus infections.