SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity.

SARS-CoV-2 uses the double-membrane vesicles as replication organelles. However, how virion assembly occurs has not been fully understood. Here we identified a SARS-CoV-2-driven membrane structure named the 3a dense body (3DB).

NLRP9 in innate immunity and inflammation.

The nucleotide-binding domain leucine-rich repeat containing receptors (NLRs) are a family of evolutionarily conserved proteins. Several members of NLRs, notably NLRP1, NLRP3 and NLRC4, are able to form cytosolic oligomeric signalling platforms termed inflammasomes to mediate immune response towards pathogens, damage and stress. However, the functions of many NLRs still remain elusive.

PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation.

The NLRP3 inflammasome, which has been linked to human inflammatory diseases, is activated by diverse stimuli. How these stimuli activate NLRP3 is unknown. Here we show that different NLRP3 stimuli lead to disassembly of the trans-Golgi network (TGN).

Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids.

Microbial infections are recognized by the innate immune system through germline-encoded pattern recognition receptors (PRRs). As most microbial pathogens contain DNA and/or RNA during their life cycle, nucleic acid sensing has evolved as an essential strategy for host innate immune defense. Pathogen-derived nucleic acids with distinct features are recognized by specific host PRRs localized in endolysosomes and the cytosol.

Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation.

Pathogens and cellular danger signals activate sensors such as RIG-I and NLRP3 to produce robust immune and inflammatory responses through respective adaptor proteins MAVS and ASC, which harbor essential N-terminal CARD and PYRIN domains, respectively. Here, we show that CARD and PYRIN function as bona fide prions in yeast and that their prion forms are inducible by their respective upstream activators. Likewise, a yeast prion domain can functionally replace CARD and PYRIN in mammalian cell signaling.

MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades.

RNA virus infections are detected by the RIG-I family of receptors, which induce type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion-like polymers that activate the cytosolic kinases IKK and TBK1, which in turn activate NF-κB and IRF3, respectively, to induce interferons. Here we show that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and TRAF6, through distinct TRAF-binding motifs.

Regulation of NF-κB by ubiquitination.

The nuclear factor κ enhancer binding protein (NF-κB) family of transcription factors regulates the expression of a large array of genes involved in diverse cellular processes including inflammation, immunity and cell survival. Activation of NF-κB requires ubiquitination, a highly conserved and versatile modification that can regulate cell signaling through both proteasome dependent and independent mechanisms. Studies in the past few years have provided new insights into the mechanisms underlying regulation of NF-κB by ubiquitination, including the involvement of multiple linkages of ubiquitin, the essential role of ubiquitin binding, and the function of unanchored polyubiquitin chains.

Direct, noncatalytic mechanism of IKK inhibition by A20.

A20 is a potent anti-inflammatory protein that inhibits NF-κB, and A20 dysfunction is associated with autoimmunity and B cell lymphoma. A20 harbors a deubiquitination enzyme domain and can employ multiple mechanisms to antagonize ubiquitination upstream of NEMO, a regulatory subunit of the IκB kinase complex (IKK). However, direct evidence of IKK inhibition by A20 is lacking, and the inhibitory mechanism remains poorly understood.

Evaluation of alternative rice planthopper control by the combined action of oil-formulated Metarhizium anisopliae and low-rate buprofezin.

Background: High resistance of brown planthopper (BPH) Nilaparvata lugens Stål to common insecticides is a challenge for control of the pest. An alternative control strategy based on the combined application of fungal and chemical agents has been evaluated.

Results: Three gradient spore concentrations of oil-formulated Metarhizium anisopliae (Metschnikoff) Sorokin (Ma456) were sprayed onto third-instar nymphs in five bioassays comprising the low buprofezin rates of 0, 10, 20, 30 and 40 µg mL(-1) respectively.

Selection of global Metarhizium isolates for the control of the rice pest Nilaparvata lugens (Homoptera: Delphacidae).

Background: This study was initiated to search for fungal candidates for microbial control of brown planthopper (BPH) Nilaparvata lugens Stål, to which little attention has been paid in the past two decades.

Results: Thirty-five isolates of Metarhizium anisopliae (Metschnikoff) Sorokin and M. flavoviride Gams & Rozsypal from different host insects worldwide were bioassayed for their lethal effects against third-instar BPH nymphs at 25 degrees C and a 14:10 h light:dark photoperiod at ca 1000 conidia mm(-2).