Structural basis for Epstein–Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins
Abstract not provided
Sathiyamoorthy, Karthik (ORCID:0000000257368709)↗
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Results for “entry”
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Monomerization of viral entry inhibitor griffithsin elucidates the relationship between multivalent binding to carbohydrates and anti-HIV activity
Mutations were introduced to the domain-swapped homodimer of the antiviral lectin griffithsin (GRFT). Whereas several single and double mutants remained dimeric, insertion of either two or four amino acids at the dimerization interface resulted in a monomeric form of the protein (mGRFT). Monomeric character of the modified proteins was confirmed by sedimentation equilibrium ultracentrifugation and by their high resolution X-ray crystal structures, whereas their binding to carbohydrates was assessed by isothermal titration calorimetry. Cell-based antiviral activity assays utilizing different variants of mGRFT indicated that the monomeric form of the lectin had greatly reduced activity against HIV-1, suggesting that the antiviral activity of GRFT stems from crosslinking and aggregation of viral particles via multivalent interactions between GRFT and oligosaccharides present on HIV envelope glycoproteins. Atomic resolution crystal structure of a complex between mGRFT and nonamannoside revealed that a single mGRFT molecule binds to two different nonamannoside molecules through all three carbohydrate-binding sites present on the monomer.
36 MATERIALS SCIENCE↗
A Mimivirus Enzyme that Participates in Viral Entry
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catalysis (homogeneous), catalysis (heterogeneous)↗
Verification of severe accident management guideline (SAMG) entry condition for OPR1000 - 367
The current severe accident prevention and mitigation strategies for OPR 1000 have emergency operating procedures (EOPs) and severe accident management guidelines (SAMGs), respectively. The main objective of SAMG is to prevent a release of radioactive materials from releasing into environment and mitigate severe accident phenomena during severe accident. The current SAMG entry condition is met when the core exit temperature (CET) reaches 650 deg. C in OPR 1000. Peak cladding temperature (PCT), which represents core integrity more precisely than CET does, cannot be used since it is not measurable in the main control room (MCR). Current SAMG entry condition for every kind of accident scenarios is not reasonable, since entry condition is determined without considering operator action time. Therefore, SAMG entry condition need to be verified with consider operator action time. Thus, an analysis methodology for SAMG entry condition was developed to verify the SAMG entry condition. A severe accident DB were also developed in order to analyze the SAMG entry condition. The analysis results of DB show that available operator action time from the SAMG entrance to RV fail is shorter than the required time in most cases. As a result, the proper SAMG entry condition was suggested through the results of DB analysis. When the SAMG entry condition is changed from CET to suggested condition, the available action time is increased about 350 to 4300 sec. Also, the suggested entry condition was verified through the simulation which considered operation action time and reflecting the suggested entry condition. (authors)
21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry
Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.
60 APPLIED LIFE SCIENCES↗
Optimizing infrasound observations for sample return capsule re-entry: Insights from OSIRIS-REx and Hayabusa2
The atmospheric entry of meteoroids presents a rare and unpredictable phenomenon, posing challenges for systematic observation and detailed characterization. Such events are nonetheless critical for advancing understanding of acoustic wave propagation, atmospheric structure, and entry dynamics. In contrast, sample return capsules (SRCs) from space missions follow well constrained re-entry trajectories, enabling planned observations of shock wave generation and propagation under controlled conditions. This study compares two SRC atmospheric entries, Hayabusa2 in 2020 and OSIRIS-REx in 2023, to assess how different infrasound array configurations influence shock wave detection and trajectory validation. Hayabusa2’s re-entry was monitored using a distributed network of 28 portable infrasound sensors across seven arrays in Woomera, Australia, permitting three-dimensional reconstruction of the trajectory and analysis of wave characteristics. For OSIRIS-REx, a compact four-sensor array deployed near Eureka Airport provided trajectory confirmation through arrival-time differences and back-azimuth estimates. Spectral and waveform analyses revealed differences in signal properties associated with variations in entry angle and velocity. The results illustrate both the strengths and the limitations of the deployed array configurations. The dense and distributed arrays during Hayabusa2’s re-entry enabled detailed trajectory reconstruction, whereas the compact array at Eureka primarily provided confirmation of signal coherence and back-azimuth consistency. These case studies highlight that even relatively small arrays, if located close to the predicted ground track, can still capture useful information on arrival direction and timing. Such insights provide practical guidance for planning future observational campaigns of SRC returns and other controlled atmospheric entries, and may also inform approaches to opportunistic observations of meteoroid events and other atmospheric acoustic phenomena.
celestial mechanics: orbit determination↗
Role of the vaccinia virus O3 protein in cell entry can be fulfilled by its Sequence flexible transmembrane domain
The vaccinia virus O3 protein, a component of the entry–fusion complex, is encoded by all chordopoxviruses. We constructed truncation mutants and demonstrated that the transmembrane domain, which comprises two-thirds of this 35 amino acid protein, is necessary and sufficient for interaction with the entry–fusion complex and function in cell entry. Nevertheless, neither single amino acid substitutions nor alanine scanning mutagenesis revealed essential amino acids within the transmembrane domain. Moreover, replication-competent mutant viruses were generated by randomization of 10 amino acids of the transmembrane domain. Of eight unique viruses, two contained only two amino acids in common with wild type and the remainder contained one or none within the randomized sequence. Although these mutant viruses formed normal size plaques, the entry–fusion complex did not co-purify with the mutant O3 proteins suggesting a less stable interaction. Thus, despite low specific sequence requirements, the transmembrane domain is sufficient for function in entry. - Highlights: • The 35 amino acid O3 protein is required for efficient vaccinia virus entry. • The transmembrane domain of O3 is necessary and sufficient for entry. • Mutagenesis demonstrated extreme sequence flexibility compatible with function.
60 APPLIED LIFE SCIENCES↗
Adaptive extension of leases for entries in a translation lookaside buffer
The described embodiments include a computing device with two or more translation lookaside buffers (TLB). During operation, the computing device updates an entry in the TLB based on a virtual address to physical address translation and metadata from a page table entry that were acquired during a page table walk. The computing device then computes, based on a lease length expression, a lease length for the entry in the TLB. Next, the computing device sets, for the entry in the TLB, a lease value to the lease length, wherein the lease value represents a time until a lease for the entry in the TLB expires, wherein the entry in the TLB is invalid when the associated lease has expired. The computing device then uses the lease value to control operations that are allowed to be performed using information from the entry in the TLB.
97 MATHEMATICS AND COMPUTING↗
C-type lectins do not act as functional receptors for filovirus entry into cells
Research highlights: {yields} Filovirus glycoprotein (GP) having a deficient receptor binding region were generated. {yields} Mutant GPs mediated virus entry less efficiently than wild-type GP. {yields} Mutant GPs bound to C-type lectins but not mediated entire steps of cellular entry. {yields} C-type lectins do not independently mediate filovirus entry into cells. {yields} Other molecule(s) are required for C-type lectin-mediated entry of filoviruses. -- Abstract: Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps of virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.
60 APPLIED LIFE SCIENCES↗
Orthopoxvirus species and strain differences in cell entry
Vaccinia virus (VACV) enters cells by a low pH endosomal route or by direct fusion with the plasma membrane. We previously found differences in entry properties of several VACV strains: entry of WR was enhanced by low pH, reduced by bafilomycin A1 and relatively unaffected by heparin, whereas entry of IHD-J, Copenhagen and Elstree were oppositely affected. Since binding and entry modes may have been selected by specific conditions of in vitro propagation, we now examined the properties of three distinct, recently isolated cowpox viruses and a monkeypox virus as well as additional VACV and cowpox virus strains. The recent isolates were more similar to WR than to other VACV strains, underscoring the biological importance of endosomal entry by orthopoxviruses. Sequence comparisons, gene deletions and gene swapping experiments indicated that viral determinants, other than or in addition to the A26 and A25 'fusion-suppressor' proteins, impact entry properties.
60 APPLIED LIFE SCIENCES↗
Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry
The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insights into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development. - Highlights: • New structural and functional insights into paramyxovirus entry mechanisms. • Current data on paramyxovirus glycoproteins suggest a core conserved entry mechanism. • Diverse mechanisms preventing premature fusion activation exist in these viruses. • Precise spacio-temporal interplay between paramyxovirus glycoproteins initiate entry.
60 APPLIED LIFE SCIENCES↗
Along-Trajectory Acoustic Signal Variations Observed During the Hypersonic Re-Entry of the OSIRIS-REx Sample Return Capsule
The re-entry of the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) sample return capsule (SRC) on 24 September 2023 presented a rare opportunity to study atmospheric entry dynamics through a dense network of ground-based infrasound sensors. As the first interplanetary capsule to re-enter over the United States since Stardust in 2006, this event allowed for unprecedented observations of infrasound signals generated during hypersonic descent. We deployed 39 single-sensor stations across Nevada and Utah, strategically distributed to capture signals from distinct trajectory points. Infrasound data were analyzed to examine how signal amplitude and period vary with altitude and propagation path for a nonablating hypersonic object with well-defined physical and aerodynamic properties. Raytracing simulations incorporated atmospheric specifications from the ground-2-space model to estimate source altitudes for observed signals. Results confirmed ballistic arrivals at all stations, with source altitudes ranging from 44 to 62 km along the trajectory. Signal period and amplitude exhibited strong dependence on source altitude, with higher altitudes corresponding to lower amplitudes, longer periods, and reduced high-frequency content. Regression analysis demonstrated strong correlations between signal characteristics and both altitude and propagation geometry. Our results suggest, when attenuation is considered, the amplitude is primarily determined by the source, with the propagation path playing a secondary role over the distances examined. These findings emphasize the utility of controlled SRC re-entries for advancing our understanding of natural meteoroid dynamics, refining atmospheric entry models, and improving methodologies for planetary defense. The OSIRIS-REx SRC campaign represents the most comprehensive infrasound study of a hypersonic re-entry to date, showcasing the potential of coordinated geophysical observational networks for high-energy atmospheric phenomena, including space debris re-entries.
58 GEOSCIENCES↗
Stress Testing of the Philips 60W Replacement Lamp L Prize Entry
The Pacific Northwest National Laboratory, operated by Battelle for the U.S. Department of Energy, worked with Intertek to develop a procedure for stress testing medium screw-base light sources. This procedure, composed of alternating stress cycles and performance evaluation, was used to qualitatively compare and contrast the durability and reliability of the Philips 60W replacement lamp L Prize entry with market-proven compact fluorescent lamps (CFLs) with comparable light output and functionality. The stress cycles applied simultaneous combinations of electrical, thermal, vibration, and humidity stresses of increasing magnitude. Performance evaluations measured relative illuminance, x chromaticity and y chromaticity shifts after each stress cycle. The Philips L Prize entry lamps appear to be appreciably more durable than the incumbent energy-efficient technology, as represented by the evaluated CFLs, and with respect to the applied stresses. Through the course of testing, all 15 CFL samples permanently ceased to function as a result of the applied stresses, while only 1 Philips L Prize entry lamp exhibited a failure, the nature of which was minor, non-destructive, and a consequence of a known (and resolved) subcontractor issue. Given that current CFL technology appears to be moderately mature and no Philips L Prize entry failures could be produced within the stress envelope causing 100 percent failure of the benchmark CFLs, it seems that, in this particular implementation, light-emitting diode (LED) technology would be much more durable in the field than current CFL technology. However, the Philips L Prize entry lamps used for testing were carefully designed and built for the competition, while the benchmark CFLs were mass produced for retail sale—a distinction that should be taken into consideration. Further reliability testing on final production samples would be necessary to judge the extent to which the results of this analysis apply to production versions of the Philips L Prize entry.
L Prize↗
ABLATION AND CHEMICAL ALTERATION OF COSMIC DUST PARTICLES DURING ENTRY INTO THE EARTH’S ATMOSPHERE
Most dust-sized cosmic particles undergo ablation and chemical alteration during atmospheric entry, which alters their original properties. A comprehensive understanding of this process is essential in order to decipher their pre-entry characteristics. The purpose of the study is to illustrate the process of vaporization of different elements for various entry parameters. The numerical results for particles of various sizes and various zenith angles are treated in order to understand the changes in chemical composition that the particles undergo as they enter the atmosphere. Particles with large sizes (> few hundred μ m) and high entry velocities (>16 km s{sup −1}) experience less time at peak temperatures compared to those that have lower velocities. Model calculations suggest that particles can survive with an entry velocity of 11 km s{sup −1} and zenith angles (ZA) of 30°–90°, which accounts for ∼66% of the region where particles retain their identities. Our results suggest that the changes in chemical composition of MgO, SiO{sub 2}, and FeO are not significant for an entry velocity of 11 km s{sup −1} and sizes <300 μ m, but the changes in these compositions become significant beyond this size, where FeO is lost to a major extent. However, at 16 km s{sup −1} the changes in MgO, SiO{sub 2}, and FeO are very intense, which is also reflected in Mg/Si, Fe/Si, Ca/Si, and Al/Si ratios, even for particles with a size of 100 μ m. Beyond 400 μ m particle sizes at 16 km s{sup −1}, most of the major elements are vaporized, leaving the refractory elements, Al and Ca, suspended in the troposphere.
79 ASTRONOMY AND ASTROPHYSICS↗
Mapping entry invalidation
A memory access system may include a first memory address translator, a second memory address translator and a mapping entry invalidator. The first memory address translator translates a first virtual address in a first protocol of a memory access request to a second virtual address in a second protocol and tracks memory access request completions. The second memory address translator is to translate the second virtual address to a physical address of a memory. The mapping entry invalidator requests invalidation of a first mapping entry of the first mapping address translator requests invalidation of a second mapping entry of the second memory address translator corresponding to the first mapping entry following invalidation of the first mapping entry and based upon the tracked memory access request completions.
Walker, Shawn K.↗