Conserved Motifs within Ebola and Marburg Virus VP40 Proteins Are Important for Stability, Localization, and Subsequent Budding of Virus-Like Particles

Liu, Yuliang; Cocka, Luis; Okumura, Atsushi; Zhang, Yong-An; Sunyer, J. Oriol; Harty, Ronald N.

doi:10.1128/jvi.02034-09

Cited by 50 publications

(64 citation statements)

References 55 publications

(84 reference statements)

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“…Indeed, there is evidence that mCherry-actin coordinates the movement and assembly of partially assembled VLPs as determined by live-cell single-particle tracking experiments [19]. During the late stages of viral replication, VP40 has been shown to interact with the endosomal sorting complex required for transport (ESCRT) machinery via its two overlapping L-domain motifs, PTAP and PPxY [3,13,20,21], as well as through a recently discovered third Ldomain motif, YPxL/I [12••], to mediate scission from the cell. There is also evidence that VP40 requires posttranslational modifications by the host cell as tyrosine-13 phosphorylation via c-Abl1 is necessary for efficient release of VLPs and productive replication of the EBOV [22].…”

Section: Vp40 Interacts With Several Important Host Protein Componentsmentioning

confidence: 99%

The Ebola Virus Matrix Protein VP40 Interacts With Several Host Protein Networks to Facilitate Viral Replication

Frick

Stahelin

2015

Curr Clin Micro Rpt

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The Ebola virus (EBOV) is a lipid-enveloped virus that is filamentous in shape and belongs to the Filoviridae family. EBOV can cause viral hemorrhagic fever in humans and non-human primates with high rates of fatality. Using a negative sense RNA genome that encodes just eight proteins, the lipid-enveloped EBOV can enter mammalian cells and undergo efficient replication to produce more virions to sustain and spread the infection. Throughout the replication cycle, EBOV inhibits or hijacks several host protein networks to suppress the immune response and to enhance the efficiency of assembly and budding from the host cell plasma membrane. Assembly and budding of EBOV is regulated by its matrix protein VP40, which can form different structures with distinct functions in the viral life cycle. VP40 has been shown to interact with several important host proteins, and although the conformational regulation of these interactions is mostly unknown, the sites of interaction have been somewhat resolved and will serve as the basis of this review article.

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Section: Vp40 Interacts With Several Important Host Protein Componentsmentioning

confidence: 99%

The Ebola Virus Matrix Protein VP40 Interacts With Several Host Protein Networks to Facilitate Viral Replication

Frick

Stahelin

2015

Curr Clin Micro Rpt

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“…VP40 budding is inhibited by tetherin in a species-specific manner. A critical step in the release of filovirus particles from the cell surface is the localization of VP40 to the plasma membrane (21,32). To assess whether amino acid changes acquired during mouse adaptation altered VP40 intracellular distribution, Huh7 cells were transfected with RAVV VP40 or maRAVV VP40.…”

Section: Maravv Vp40 Fails To Bud Efficiently From Human Cell Linesmentioning

confidence: 99%

“…For MARV VP40, the late domain PPPY asso-ciates with Tsg101 and Nedd4 (19,20). In addition, amino acid sequences in VP40 located downstream of the traditional late domain motifs, including the motif LPLGIM, also influence budding (21). In the absence of these motifs, VLP release is reduced as VP40 oligomerization and plasma membrane localization are altered (21).…”

mentioning

confidence: 99%

“…In addition, amino acid sequences in VP40 located downstream of the traditional late domain motifs, including the motif LPLGIM, also influence budding (21). In the absence of these motifs, VLP release is reduced as VP40 oligomerization and plasma membrane localization are altered (21). A host factor that can impair VP40 budding is tetherin/ bone marrow stromal cell antigen 2 (BST-2)/CD317.…”

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confidence: 99%

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The VP40 Protein of Marburg Virus Exhibits Impaired Budding and Increased Sensitivity to Human Tetherin following Mouse Adaptation

Feagins

Basler

2014

J Virol

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The Marburg virus VP40 protein is a viral matrix protein that spontaneously buds from cells. It also functions as an interferon (IFN) signaling antagonist by targeting Janus kinase 1 (JAK1). A previous study demonstrated that the VP40 protein of the Ravn strain of Marburg virus (Ravn virus [RAVV]) failed to block IFN signaling in mouse cells, whereas the mouse-adapted RAVV (maRAVV) VP40 acquired the ability to inhibit IFN responses in mouse cells. The increased IFN antagonist function of maRAVV VP40 mapped to residues 57 and 165, which were mutated during the mouse adaptation process. In the present study, we demonstrate that maRAVV VP40 lost the capacity to efficiently bud from human cell lines, despite the fact that both parental and maRAVV VP40s bud efficiently from mouse cell lines. The impaired budding in human cells corresponds with the appearance of protrusions on the surface of maRAVV VP40-expressing Huh7 cells and with an increased sensitivity of maRAVV VP40 to restriction by human tetherin but not mouse tetherin. However, transfer of the human tetherin cytoplasmic tail to mouse tetherin restored restriction of maRAVV VP40. Residues 57 and 165 were demonstrated to contribute to the failure of maRAVV VP40 to bud from human cells, and residue 57 was demonstrated to alter VP40 oligomerization, as assessed by coprecipitation assay, and to determine sensitivity to human tetherin. This suggests that RAVV VP40 acquired, during adaptation to mice, changes in its oligomerization potential that enhanced IFN antagonist function. However, this new capacity impaired RAVV VP40 budding from human cells. IMPORTANCEFiloviruses, which include Marburg viruses and Ebola viruses, are zoonotic pathogens that cause severe disease in humans and nonhuman primates but do not cause similar disease in wild-type laboratory strains of mice unless first adapted to these animals. Although mouse adaptation has been used as a method to develop small animal models of pathogenesis, the molecular determinants associated with filovirus mouse adaptation are poorly understood. Our study demonstrates how genetic changes that accrued during mouse adaptation of the Ravn strain of Marburg virus have impacted the budding function of the viral VP40 matrix protein. Strikingly, we find impairment of mouse-adapted VP40 budding function in human but not mouse cell lines, and we correlate the impairment with an increased sensitivity of VP40 to restriction by human but not mouse tetherin and with changes in VP40 oligomerization. These data suggest that there are functional costs associated with filovirus adaptation to new hosts and implicate tetherin as a filovirus host restriction factor.

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“…In typical atom cooling, the interrogation and detection of a compact cold atom clock are conducted in same zone. Thus, decoherence during evolution is an important factor.Coherence during evolution is affected by several factors, such as atom collision, external electromagnetic field, temperature and density of atomic samples [8,9] , and others. Generally, decoherence time is described by transverse decay rate, which can be determined through an experiment.…”

mentioning

confidence: 99%

Ramsey interaction with transverse decay

Wang¹,

Cheng²,

Liu³

2012

中国光学快报

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The Ramsey fringe contrast of a pulsed optically pumped cold atom clock is strongly affected by the transverse decay of the atomic sample. This letter calculates the Ramsey fringe with focus on transverse decay, and analyzes the Ramsey fringe contrast with different transverse decay rates. By fitting the experimental data, we obtain the transverse decay rate in a cold atom sample at an approximate value of 30.5 s −1 , which is much smaller than that in a cell. OCIS codes: 020.0020, 270.0270. doi: 10.3788/COL201210.100201.A typical microwave atomic clock uses the transition between two ground states as signal to lock the local oscillator. The spectral width, signal-to-noise ratio (SNR), and contrast are the key factors determining clock performance. The width is directly related to the interaction duration between the atoms and the microwave. The Ramsey method has been widely used in microwave beam clocks [1] and, recently, in cell or cold atom clocks. A typical cesium beam clock has two microwave cavities separated by L, and a cesium beam passes through the cavities with speed v [2] . The width of the Ramsey fringe is determined by T = L/v. Similarly, the atomic fountain [3] uses a single cavity but passes twice during the upward and downward motions of the cold atoms.The Ramsey fringe contrast is affected by decoherence during the evolution of atoms between two Ramsey pulses. Theoretically, however, contrast is not considered in the cesium beam clock, because the coherence time is longer than the evolution time, which is similar in the atomic fountain clock [3] . Recently, compact cold atom clocks have received considerable attention due to their potential applications [4−7] . The compact cold atom clock has small volume, low weight, and high performance properties. In typical atom cooling, the interrogation and detection of a compact cold atom clock are conducted in same zone. Thus, decoherence during evolution is an important factor.Coherence during evolution is affected by several factors, such as atom collision, external electromagnetic field, temperature and density of atomic samples [8,9] , and others. Generally, decoherence time is described by transverse decay rate, which can be determined through an experiment.In this letter, we introduce a transverse decay rate, γ, to describe decoherence in the evolution between two Ramsey pulses. We also study the Ramsey fringe contrast resulting from γ and compared it with experimental result. Finally, we estimate γ by fitting the experimental data with theory.The up and down levels of a two-level atom system are represented by |1 and |2 , respectively. The density matrix is expressed asThe hyperfine states that |1 and |2 have eigenvalues of E 1 and E 2 , respectively, and E 1 − E 2 = ω 0 , ω 0 is the hyperfine transition frequency between states |1 and |2 . The interaction between a two-level atom and a microwave field is described by the optical Bloch equations [10] given bywhere the perturbation term V 12 is expressed asand ω is the frequency of the microwave f...

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Conserved Motifs within Ebola and Marburg Virus VP40 Proteins Are Important for Stability, Localization, and Subsequent Budding of Virus-Like Particles

Cited by 50 publications

References 55 publications

The Ebola Virus Matrix Protein VP40 Interacts With Several Host Protein Networks to Facilitate Viral Replication

The Ebola Virus Matrix Protein VP40 Interacts With Several Host Protein Networks to Facilitate Viral Replication

The VP40 Protein of Marburg Virus Exhibits Impaired Budding and Increased Sensitivity to Human Tetherin following Mouse Adaptation

Ramsey interaction with transverse decay

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