African swine fever virus (ASFV) is a giant and complex DNA virus that causes a highly contagious and often lethal swine disease for which no vaccine is available. Using an optimized image ...reconstruction strategy, we solved the ASFV capsid structure up to 4.1 angstroms, which is built from 17,280 proteins, including one major (p72) and four minor (M1249L, p17, p49, and H240R) capsid proteins organized into pentasymmetrons and trisymmetrons. The atomic structure of the p72 protein informs putative conformational epitopes, distinguishing ASFV from other nucleocytoplasmic large DNA viruses. The minor capsid proteins form a complicated network below the outer capsid shell, stabilizing the capsid by holding adjacent capsomers together. Acting as core organizers, 100-nanometer-long M1249L proteins run along each edge of the trisymmetrons that bridge two neighboring pentasymmetrons and form extensive intermolecular networks with other capsid proteins, driving the formation of the capsid framework. These structural details unveil the basis of capsid stability and assembly, opening up new avenues for African swine fever vaccine development.
Influenza virus infection is dependent on host cellular factors, and identification of these factors and their underlying mechanisms can provide important information for the development of ...strategies to inhibit viral infection. Here, we used a highly pathogenic H5N1 influenza virus to perform a genome-wide CRISPR/Cas9 gene knockout screen in human lung epithelial cells (A549 cells), and found that knockout of transmembrane protein immunoglobulin superfamily DCC subclass member 4 (IGDCC4) significantly reduced the replication of the virus in A549 cells. Further studies showed that IGDCC4 interacted with the viral hemagglutinin protein and facilitated virus internalization into host cells. Animal infection studies showed that replication of H5N1 virus in the nasal turbinates, lungs, and kidneys of IGDCC4-knockout mice was significantly lower than that in the corresponding organs of wild-type mice. Half of the IGDCC4-knockout mice survived a lethal H5N1 virus challenge, whereas all of the wild-type mice died within 11 days of infection. Our study identifies a novel host factor that promotes influenza virus infection by facilitating internalization and provides insights that will support the development of antiviral therapies.
Inflammatory factors and type I interferons (IFNs) are key components of host antiviral innate immune responses, which can be released from the pathogen-infected macrophages. African swine fever ...virus (ASFV) has developed various strategies to evade host antiviral innate immune responses, including alteration of inflammatory responses and IFNs production. However, the molecular mechanism underlying inhibition of inflammatory responses and IFNs production by ASFV-encoded proteins has not been fully understood. Here we report that ASFV infection only induced low levels of IL-1β and type I IFNs in porcine alveolar macrophages (PAMs), even in the presence of strong inducers such as LPS and poly(dA:dT). Through further exploration, we found that several members of the multigene family 360 (MGF360) and MGF505 strongly inhibited IL-1β maturation and IFN-β promoter activation. Among them, pMGF505-7R had the strongest inhibitory effect. To verify the function of pMGF505-7R
in vivo
, a recombinant ASFV with deletion of the MGF505-7R gene (ASFV-Δ7R) was constructed and assessed. As we expected, ASFV-Δ7R infection induced higher levels of IL-1β and IFN-β compared with its parental ASFV HLJ/18 strain. ASFV infection-induced IL-1β production was then found to be dependent on TLRs/NF-κB signaling pathway and NLRP3 inflammasome. Furthermore, we demonstrated that pMGF505-7R interacted with IKKα in the IKK complex to inhibit NF-κB activation and bound to NLRP3 to inhibit inflammasome formation, leading to decreased IL-1β production. Moreover, we found that pMGF505-7R interacted with and inhibited the nuclear translocation of IRF3 to block type I IFN production. Importantly, the virulence of ASFV-Δ7R is reduced in piglets compared with its parental ASFV HLJ/18 strain, which may due to induction of higher IL-1β and type I IFN production
in vivo
. Our findings provide a new clue to understand the functions of ASFV-encoded pMGF505-7R and its role in viral infection-induced pathogenesis, which might help design antiviral agents or live attenuated vaccines to control ASF.
In distributed manufacturing systems, especially in a manufacturing grid (MGrid) system, there are primarily two kinds of manufacturing tasks (or resource service requests): (1) single resource ...service request task (SRSRTask), which can be completed by invoking only one resource service, and (2) multi-resource service request task (MRSRTask), which is completed by invoking several resource services in a certain sequence. For an SRSRTask, the system searches the resource services that are qualified for its function requirements and chooses the optimal one to execute it. For an MRSRTask, in addition to the search for all qualified resource services according to each subtask, the system selects one candidate resource service for each subtask. Then the system generates a new composite resource service (CRS) and selects the optimal resource service composite path from all possible paths to execute the task with the given multi-objective (e.g., time minimization, cost minimization, and reliability maximization) and constraints. The above problem is defined as multi-objective MGrid resource service composition and optimal-selection (MO-MRSCOS) problem in this paper. The formulation is presented for an MO-MRSCOS problem to minimize execution time and cost, and maximize the reliability. The basic resource service composite modes (RSCM) for CRS are described, and the principles for translating a complicated RSCM into a simple sequence RSCM are presented for simplifying the resolving process and complexity of MO-MRSCOS. A new MGrid resource service composition and optimal-selection method, based on the principles of particle swarm optimization (PSO), is then proposed. The PSO follows a collaborative population-based search, which models based on the social behavior of bird flocking and fish schooling. The case study demonstrates that the proposed method is useful in solving MO-MRSCOS problems. The experimental results and performance comparison show that the proposed method is both effective and efficient.
For a multi-resource service request task (MRSRTask) in manufacturing grid (MGrid) system, in addition to the search for all qualified resource services according to each subtask, the system selects ...one candidate resource service for each subtask. Then the system generates a new composite resource service (CRS) and selects the optimal resource service composite path from all possible paths to execute the task with the given multi-objective (e.g., time minimization, cost minimization and reliability maximization) and multi-constraints. The above problem is defined as multi-objective MGrid resource service composition and optimal-selection (MO-MRSCOS) problem. The formulation is presented for an MO-MRSCOS problem. The correlations among resource services are taken into account during MGrid resource service composition, and a QoS description mode supporting resource service correlation is presented. The basic resource service composite modes (RSCM) for CRS are described, and the principles for translating a complicated RSCM into a simple sequence RSCM are presented for simplifying the resolving process and complexity of MO-MRSCOS problem. A new method based on the principles of particle swarm optimization (PSO), is proposed for solving MO-MRSCOS problem. Unlike previous works: (a) the proposed PSO algorithms combine the non-dominated sorting technique to achieve the selection of global best position and private best position; (b) the parameters of particle updating formulation in PSO are dynamical generated in order to make a compromise between the global exploration and local exploitation abilities of PSO; (c)
permutation-based and
objective-based population trimming operators are applied in PSO to maintain diversity of solutions in population. The experimental results and performance comparison show that the proposed method is both effective and efficient.
A novel tyrosinase biosensor based on Fe(3)O(4) nanoparticles-chitosan nanocomposite has been developed for the detection of phenolic compounds. The large surface area of Fe(3)O(4) nanoparticles and ...the porous morphology of chitosan led to a high loading of enzyme and the entrapped enzyme could retain its bioactivity. The tyrosinase-Fe(3)O(4) nanoparticle-chitosan bionanocomposite film was characterized with atomic force microscopy and AC impedance spectra. The prepared biosensor was used to determine phenolic compounds by amperometric detection of the biocatalytically liberated quinone at -0.2V vs. saturated calomel electrode (SCE). The different parameters, including working potential, pH of supporting electrolyte and temperature that governs the analytical performance of the biosensor have been studied in detail and optimized. The biosensor was applied to detect catechol with a linear range of 8.3 x 10(-8) to 7.0 x 10(-5)mol L(-1), and the detection limit of 2.5 x 10(-8)mol L(-1). The tyrosinase biosensor exhibits good repeatability and stability. Such new tyrosinase biosensor shows great promise for rapid, simple, and cost-effective analysis of phenolic contaminants in environmental samples. The proposed strategy can be extended for the development of other enzyme-based biosensors.
African swine fever (ASF) entered China in August 2018 and rapidly spread across the entire country, severely threatening the Chinese domestic pig population, which accounts for more than 50% of the ...pig population worldwide. In this study, an ASFV isolate, Pig/Heilongjiang/2018 (Pig/HLJ/18), was isolated in primary porcine alveolar macrophages (PAMs) from a pig sample from an ASF outbreak farm. The isolate was characterized by using the haemadsorption (HAD) test, Western blotting and immunofluorescence, and electronic microscopy. Phylogenetic analysis of the viral p72 gene revealed that Pig/HLJ/18 belongs to Genotype II. Infectious titres of virus propagated in primary PAMs and pig marrow macrophages were as high as 10
7.2
HAD
50
/ml. Specific-pathogen-free pigs intramuscularly inoculated with different virus dosages at 10
3.5
-10
6.5
HAD
50
showed acute disease with fever and haemorrhagic signs. The incubation periods were 3-5 days for virus-inoculated pigs and 9 days for contact pigs. All virus-inoculated pigs died between 6-9 days post-inoculation (p.i.), and the contact pigs died between 13-14 days post-contact (p.c.). Viremia started on day 2 p.i. in inoculated pigs and on day 9 p.c. in contact pigs. Viral genomic DNA started to be detected from oral and rectal swab samples on 2-5 days p.i. in virus-inoculated pigs, and 6-10 days p.c. in contact pigs. These results indicate that Pig/HLJ/18 is highly virulent and transmissible in domestic pigs. Our study demonstrates the threat of ASFV and emphasizes the need to control and eradicate ASF in China.
African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of ...different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF_505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry.
In itinerant magnetic systems, a spin density wave (SDW) state can be induced by Fermi surface nesting and electron-electron interaction. It may intertwine with other orders such as charge density ...wave (CDW), while their relation is still yet to be understood. Here via spin-polarized scanning tunneling microscopy, we directly observed long-range spin modulation on Cr(001) surface, which corresponds to the well-known incommensurate SDW of bulk Cr. It displays 6.0 nm in-plane period and anti-phase behavior between adjacent (001) planes. Meanwhile, we simultaneously observed the coexisting CDW with half the period of SDW. Such SDW/CDW have highly correlated domain structures and are in-phase. Surprisingly, the CDW displays a contrast inversion around a density-of-states dip at -22 meV, indicating an anomalous CDW gap opened below E
. These observations support that the CDW is a secondary order driven by SDW. Our work is not only a real-space characterization of incommensurate SDW, but also provides insights on how SDW and CDW coexist.
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