T W Geisbert

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..Together, these data suggest that coagulation abnormalities associated with EBOV HF are not the direct result of EBOV-induced cytolysis of endothelial cells, and are likely triggered by immune-mediated mechanisms...

..Here, we describe the development of a potential therapy for EBOV infection that is based on small interfering RNAs (siRNAs)...

..Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge...

..Of equal importance, these comparisons highlight critical gaps in our knowledge of these pathogens...

..This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection...

..This review takes a brief historic look at attempts to develop an efficacious vaccine, provides an overview of current vaccine candidates and highlights strategies that have the greatest potential for commercial development...

..Here, we tested the notion that blockade of fVIIa/tissue factor is beneficial after infection with Ebola virus...

..Thus, chemotherapeutic strategies aimed at controlling overexpression of TF may ameliorate the effects of EBOV hemorrhagic fever...

..The sequence of pathogenetic events identified in this study should provide new targets for rational prophylactic and chemotherapeutic interventions...

..The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms...

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..Taken together with in vivo observations that early deaths were not observed in animals immunized with various viral vectors expressing EBOV GP, it is unlikely that any EBOV-enhancing antibodies profoundly affected EBOV pathogenesis...

..Effective treatment of Ebola infections may require a combination of drugs that inhibit viral replication in monocyte/macrophage-like cells while reversing the pathologic effects (e.g., coagulopathy) consequent to this replication...

..Intact virions and typical arenavirus inclusions were demonstrated by immunoelectron microscopy in these tissues. Based on these findings, the guinea pig appears to be a valid animal model of the human disease...

..The availability of immunodeficient, "gene-knockout" and transgenic mice will make the mouse model particularly useful for studying the early steps of Ebola pathogenesis...

..These data suggest that the VSVDeltaG/MARVGP-Musoke vaccine should be sufficient to protect against all known MARV strains...

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..Concurrent bacterial septicemia, present in one monkey, was associated with increased dissemination of the virus to the liver, spleen, and bone marrow and resulted in a more rapidly fatal clinical course...

..GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine...

..In a mouse model of ZEBOV infection, lymphocyte death is a prominent finding; however, the mechanism of death and the lymphocyte subsets that are targeted remain unknown...

..IL-6 production was detected late in the infection in CD14(+) spleen cells. These results suggest a robust innate immune response to MARV; however, this response was delayed relative to the infection...

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..Here, we report that recombinant human interferon-beta 1a potently inhibits SARS coronavirus replication in vitro...

..Identification of cytokine/chemokine, nitric oxide, and reactive oxygen species involvement in the observed filoviral pathogenesis may lend insight into the rational design of therapeutic countermeasures of filoviral pathogenesis...

..These results validated that Hsp90 is an important host factor for the replication of filoviruses and suggest that Hsp90 inhibitors may be therapeutically effective in treating EBOV infection...

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..In this review, select technologies and approaches will be highlighted as part of the critical path for the development of therapeutics to ameliorate the invariably devastating outcomes of human filoviral infections...

..This case demonstrates the value of transmission electron microscopy as a tool for assisting in the definitive diagnosis of Marburg or Ebola hemorrhagic fever, as well as providing insight into the pathogenesis of these agents...

..The aim of this study was to test the efficacy of rhAPC as a potential treatment for ZHF...

..These data cast further doubt on the value of passive immunotherapy for the treatment of EBOV infection...

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..Some of the remaining and key unanswered questions relating to the role of the vascular system in the pathogenesis of this disease, that need to be addressed in further research, are highlighted...

..We aimed to test the efficacy of a replication-competent vaccine based on attenuated recombinant vesicular stomatitis virus (rVSV), as a postexposure treatment for MARV haemorrhagic fever...

..We suggest that treatment extended the time course of the disease and permitted the virus to infect tissues not usually affected in the typical model...

..In addition, substantial progress has been made in developing recombinant vaccines against these viruses...

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..These data suggest that GP lacking the ADE-inducing epitopes may increase the potential of GP as a vaccine antigen...

..These results provide a detailed picture of the host transcriptional response during smallpox infection, and may help guide the development of diagnostic, therapeutic, and prophylactic strategies...

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..Here, we review the present literature on treatment and pathogenesis of LF and outline priorities for future research in the field made possible by the improved research capacity of the MRU LFN...

..This is the first demonstration of complete postexposure protection against an Ebola virus in nonhuman primates and provides further evidence that postexposure vaccination may have utility in treating exposures to filoviruses...

..This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses...

..These findings demonstrate that the incorporation of a foreign gene will attenuate ZEBOV in vivo but that these viruses still have potential for in vitro and in vivo research applications...

..These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival...

..quot; A summary of the opportunities for and challenges to improving treatment of filovirus hemorrhagic fevers is presented here...

..In summary, the study provides new insight into the M. fascicularis V region gene repertoire and further supports the idea that macaque-derived mAbs may be of therapeutic value to humans...

..It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody...

..In particular, a vaccine based on attenuated recombinant vesicular stomatitis virus was recently shown to have both preventive and postexposure efficacy...

..No evidence of EBOV or MARV replication was detected in any of the protected animals after challenge. Our data suggest that these vaccine candidates are safe and highly efficacious in a relevant animal model...

..Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo...

..We conclude that glycoprotein cleavage by subtilisin-like endoproteases is not critical for Ebola virus infectivity and virulence in nonhuman primates...

..While significant progress has been made over the last several years in dissecting out the molecular biology and pathogenesis of the HF viruses, there are currently no vaccines or drugs licensed available for most of the VHFs...

..We describe a diagnostic system for rapid, multiplex polymerase chain reaction identification of 10 different causes of viral hemorrhagic fevers...

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