Ebola Virus VP40 Drives the Formation of Virus-Like Filamentous Particles Along with GP

Noda, Takeshi; Sagara, Hiroshi; Suzuki, Emiko; Takada, Ayato; Kida, Hiroshi; Kawaoka, Yoshihiro

doi:10.1128/jvi.76.10.4855-4865.2002

Cited by 336 publications

(342 citation statements)

References 35 publications

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“…VP40 functions as a matrix protein and is responsible for the formation of the filamentous particles (Ref. 22). VP24 is a minor viral protein whose functions remain unknown, but recent data indicate that VP24 possesses structural features consistent with a function as a viral matrix protein and suggest that VP24 might have a role in viral assembly and budding (Refs 23,24,25).…”

Section: Ebov: Structure and Protein Functionsmentioning

confidence: 99%

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Geisbert

Hensley

2004

Expert Rev. Mol. Med.

112

106

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Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicised isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV 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. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. 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.

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Section: Ebov: Structure and Protein Functionsmentioning

confidence: 99%

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Geisbert

Hensley

2004

Expert Rev. Mol. Med.

112

106

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“…VeroVP30 cells were infected with Ebola⌬VP30-neo virus and fixed 36 h later. Samples were processed for TEM as described (14). As shown in Fig.…”

Section: Genetic Stability Of Ebola⌬vp30-neo Virusmentioning

confidence: 99%

“…The lack of sufficient BSL-4 space and trained personnel and the rigors of working in BSL-4 laboratories have severely hampered basic research with EBOVs as well as the development of vaccines and large-scale screening for effective antiviral compounds. These limitations have prompted examination of various steps in the EBOV viral life cycle in the absence of infectious virus: (i) replication and transcription were studied by use of reporter gene assays that are based on the expression of necessary viral components from plasmids (3-7); (ii) entry and fusion processes were assessed with pseudotyping assays that rely on the use of recombinant vesicular stomatitis or retroviruses (8 -11); and (iii) budding was examined by using virus-like particles that are generated from viral proteins provided by protein expression plasmids (12)(13)(14)(15)(16). However, several recent findings suggest that data obtained with these artificial systems may not always be reproducible with live, authentic EBOV (17).…”

mentioning

confidence: 99%

Generation of biologically contained Ebola viruses

Halfmann

Kim

Ebihara

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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119

163

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Ebola virus (EBOV), a public health concern in Africa and a potential biological weapon, is classified as a biosafety level-4 agent because of its high mortality rate and the lack of approved vaccines and antivirals. Basic research into the mechanisms of EBOV pathogenicity and the development of effective countermeasures are restricted by the current biosafety classification of EBOVs. We therefore developed biologically contained EBOV that express a reporter gene instead of the VP30 gene, which encodes an essential transcription factor. A Vero cell line that stably expresses VP30 provides this essential protein in trans and biologically confines the virus to its complete replication cycle in this cell line. This complementation approach is highly efficient because biologically contained EBOVs lacking the VP30 gene grow to titers similar to those obtained with wild-type virus. Moreover, EBOVs lacking the VP30 gene are indistinguishable in their morphology from wild-type virus and are genetically stable, as determined by sequence analysis after seven serial passages in VP30-expressing Vero cells. We propose that this system provides a safe means to handle EBOV outside a biosafety level-4 facility and will stimulate critical studies on the EBOV life cycle as well as large-scale screening efforts for compounds with activity against this lethal virus.antiviral screening ͉ reverse genetics ͉ vaccine development

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“…Ebola VLP (eVLP) and Marburg VLP self-assemble and bud from cellular lipid rafts following expression of GP and VP40 in mammalian cells (27)(28)(29)(30)(31)(32). Mice and guinea pigs vaccinated with eVLPs are completely protected from lethal EBOV challenge (28,29,33); therefore, eVLPs represent a promising vaccine candidate for prevention of lethal EBOV infections.…”

mentioning

confidence: 99%

Induction of Humoral and CD8+ T Cell Responses Are Required for Protection against Lethal Ebola Virus Infection

Warfield

Olinger

Deal

et al. 2005

The Journal of Immunology

127

142

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Ebola virus (EBOV)-like particles (eVLP), composed of the EBOV glycoprotein and matrix viral protein (VP)40 with a lipid membrane, are a highly efficacious method of immunization against EBOV infection. The exact requirements for immunity against EBOV infection are poorly defined at this time. The goal of this work was to determine the requirements for EBOV immunity following eVLP vaccination. Vaccination of BALB/c or C57BL/6 mice with eVLPs in conjunction with QS-21 adjuvant resulted in mixed IgG subclass responses, a Th1-like memory cytokine response, and protection from lethal EBOV challenge. Further, this vaccination schedule led to the generation of both CD4+ and CD8+ IFN-γ+ T cells recognizing specific peptides within glycoprotein and VP40. The transfer of both serum and splenocytes, but not serum or splenocytes alone, from eVLP-vaccinated mice conferred protection against lethal EBOV infection in these studies. B cells were required for eVLP-mediated immunity to EBOV because B cell-deficient mice vaccinated with eVLPs were not protected from lethal EBOV challenge. We also found that CD8+, but not CD4+, T cells are absolutely required for eVLP-mediated protection against EBOV infection. Further, eVLP-induced protective mechanisms were perforin-independent, but IFN-γ-dependent. Taken together, both EBOV-specific humoral and cytotoxic CD8+ T cell responses are critical to mediate protection against filoviruses following eVLP vaccination.

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Ebola Virus VP40 Drives the Formation of Virus-Like Filamentous Particles Along with GP

Cited by 336 publications

References 35 publications

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Generation of biologically contained Ebola viruses

Induction of Humoral and CD8+ T Cell Responses Are Required for Protection against Lethal Ebola Virus Infection

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