| 1. |
- Chan, Yi-Hao, et al.
(författare)
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Human TMEFF1 is a restriction factor for herpes simplex virus in the brain
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 632, s. 390-400
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Tidskriftsartikel (refereegranskat)abstract
- Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE. A study of two childhood cases of herpes simplex encephalitis shows that TMEFF1 interacts with the HSV-1 cell-surface receptor NECTIN-1, preventing HSV-1 from fusing with the cell membrane and entering cortical neurons.
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| 2. |
- Migeon, Sebastien, et al.
(författare)
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Post-failure Processes on the Continental Slope of the Central Nile Deep-Sea Fan : Interactions Between Fluid Seepage, Sediment Deformation and Sediment-Wave Construction
- 2014
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Ingår i: Submarine Mass Movements and their Consequences. - Cham : Springer. - 9783319009728 - 9783319009711 ; , s. 117-127
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Konferensbidrag (refereegranskat)abstract
- Voluminous mass-transport deposits (MTD) have been identified on seismic profiles across the central Nile Deep-Sea Fan (NDSF). The youngest MTDs are buried under 30-100 m of well-stratified slope deposits that, in water depths of 1,800-2,600 m, are characterized by undulating reflectors correlated with slope-parallel seabed ridges and troughs. Seabed imagery shows that, in the western part of the central NDSF, short, arcuate undulations are associated with fluid venting (carbonate pavements, gas flares), while to the east, long, linear undulations have erosional furrows on their downslope flanks and fluid seeps are less common. Sub-bottomprofiles suggest that the western undulations correspond to rotated fault-blocks above the buried MTDs, while those in the east are sediment waves generated by gravity flows. We suggest that fluids coming from dewatering of MTDs and/or from deeper layers generate overpressures along the boundary between MTDs and overlying fine-grained sediment, resulting in a slow downslope movement of the sediment cover and formation of tilted blocks separated by faults. Fluids can migrate to the seafloor, leading to the construction of carbonate pavements. Where the sediment cover stabilizes, sediment deposition by gravity flows may continue building sediment waves. These results suggest that complex processes may follow the emplacement of large MTDs, significantly impacting continental-slope evolution.
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