Ebola Virus Matrix Protein VP40 Interaction with Human Cellular Factors Tsg101 and Nedd4

Timmins, Joanna; Schoehn, Guy; Ricard‐Blum, Sylvie; Scianimanico, Sandra; Vernet, Thierry; Ruigrok, Rob W.H.; Weissenhorn, Winfríed

doi:10.1016/s0022-2836(02)01406-7

Cited by 186 publications

(186 citation statements)

References 57 publications

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“…Tsg101 has been implicated in the budding of HIV-1 and Ebola virus through its interaction with the PTAP motif present in the L domains of Gag and VP40, respectively (36,37). The PTAP motif present in LFV Z suggested its possible interaction with Tsg101.…”

Section: Intracellular Localization Of Wild-type and Mutant Z Proteinmentioning

confidence: 99%

The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies

Perez

Craven

Torre

2003

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

308

403

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By using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), we have identified the arenavirus small RING finger Z protein as the main driving force of virus budding. Both LCMV and Lassa fever virus (LFV) Z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the Gag protein of Rous sarcoma virus. LCMV and LFV Z proteins contain proline-rich motifs that are characteristic of late domains. Mutations in the PPPY motif of LCMV Z severely impaired the formation of virus-like particles. LFV Z contains two different proline-rich motifs, PPPY and PTAP, which are separated by eight amino acids. Mutational analysis revealed that both motifs are required for efficient LFV Z-mediated budding. Both LCMV and LFV Z proteins recruited to the plasma membrane Tsg101, which is a component of the class E vacuolar protein sorting machinery that has been implicated in budding of HIV and Ebola virus. A renaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever (HF) viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism (1). The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is an important model with which to study both acute and persistent viral infection (2). In addition, LCMV provides an excellent system with which to study basic aspects of the molecular and cell biology of HF arenaviruses.LCMV is an enveloped virus, whose genome consists of two negative-sense, single-stranded RNA segments, called L (7.2 kb) and S (3.4 kb). Each segment uses an ambisense coding organization to direct the synthesis of two gene products in opposite orientation, and each is separated by an intergenic region (3) The S RNA encodes the nucleoprotein (NP), and the two surface virion glycoproteins (GPs), GP-1 and GP-2, which are derived by proteolytic cleavage of a precursor polypeptide, GP-C (4). GP-1 and GP-2 form the spikes on the virion envelope and mediate cell entry by interaction with the host cell surface receptor (5). The L RNA directs the synthesis of the virus RNA-dependent RNA polymerase (L protein), and a small RING finger protein called Z (11 kDa) (6). The NP associates with the viral genomic RNA species and L to form the viral ribonucleoprotein (RNP) core that is competent in transcription and RNA replication, and constitutes the minimal infectious unit (7). The role of Z in the virus life cycle is poorly understood, and homologues of Z are not found in other negativestrand (NS) RNA viruses. Z is a structural component of the virus (8), and in infected cells, Z has been reported to interact with several cellular factors, including promyelocytic leukemia protein (9), and the eukaryotic translation initiation factor 4E, the latter of which has been proposed to repress CAP-dependent translation (10, 11). In addition, early studies suggested a role of Z in viral transcriptional regulation (12).We have developed a reverse genetic system f...

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Section: Intracellular Localization Of Wild-type and Mutant Z Proteinmentioning

confidence: 99%

The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies

Perez

Craven

Torre

2003

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

308

403

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“…EBOV budding is mediated by two proline-rich motifs -PPxY and PTAP -within VP40 ( Refs 136,137,138,139,140). A full N-terminus of VP40 is required for budding to occur efficiently (Refs 137,139).…”

Section: Budding Inhibitorsmentioning

confidence: 99%

“…A full N-terminus of VP40 is required for budding to occur efficiently (Refs 137,139). Optimal budding is facilitated by interaction with the cellular ubiquinating enzymes Nedd4 and Tsg101 (Refs 138, 139, 140).…”

Section: Budding Inhibitorsmentioning

confidence: 99%

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

Geisbert

Hensley

2004

Expert Rev. Mol. Med.

111

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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“…Moreover, sGP has many similar epitopes with GP, so it could potentially sequester or absorb host Abs to block their downstream action 54, 55 . Thus, the viral proteins disrupt different components of the immune system to attach to the host cell for subsequent entry.…”

Section: Issn: 2250-1177 [128] Coden (Usa): Jddtaomentioning

confidence: 99%

A Comprehensive Study on Ebola (Ebov) Virus: A Threat to Human Existence

Taneja

Malik²,

Singh

et al. 2018

J. Drug Delivery Ther.

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Ebola hemorrhagic disease is a severe, an acute, often fatal disease in humans and non-humans which is caused by infection with a virus of family: Filoviridae, genus: Ebola virus. The incubation period of ebola virus disease (EVD) varies from 2-21 days, with an observed average of 8 to 10 days by following introduction of Ebola virus in the human population through animal-to-human transmission, person-to-person transmission by direct contact body fluids/secretions of infected persons. The most common symptoms include sudden onset of fever, intense weakness, muscle pain, headache and sore throat, vomiting, diarrhea, rash, impaired kidney and liver function, and at advanced stage both internal and external bleeding. The virus is transmitted by contact with body fluids of infected humans or an animal is primarily responsible for the virus outbreak. Fruit bats are considered as the natural reservoirs of the virus. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer (four-fold) contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. In this review, the Ebola virus: life cycle and pathogenicity in humans, diagnosis, pharmacotherapy and their prevention is summarized.

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Ebola Virus Matrix Protein VP40 Interaction with Human Cellular Factors Tsg101 and Nedd4

Cited by 186 publications

References 57 publications

The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies

The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies

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

A Comprehensive Study on Ebola (Ebov) Virus: A Threat to Human Existence

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