查看更多>>摘要：The plant hormone salicylic acid plays an important role in balancing plant immunity and growth. In this issue of Cell Host & Microbe, Liu et al. (2022) discovered that a long non-coding RNA, lncSABC1, promotes growth in uninfected plants and unleashes defenses when pathogens attack by transcriptionally regulating salicylic acid biosynthesis.
查看更多>>摘要：In this issue of Cell Host & Microbe, Tsai et al. (2022) provide evidence that Staphylococcus aureus should be numbered among the pathogens for which original antigenic sin governs subsequent immune responses. Their approach may restore the utility of murine models in staphylococcal vaccine development.
查看更多>>摘要：In this issue of Cell Host & Microbe, Li et al. unveil an association between HLA-B*46:01 and HIV disease progression in Asian populations. The distinct natural killer (NK) cell signature identified in individuals carrying HLA-B*46:01 strongly suggests that NK cell inhibition plays a role in loss of HIV control.
查看更多>>摘要：Tackling the ancient infectious foe of malaria, Xie et al. (2022) uncover a novel class of nucleoside analogs that selectively hijack and inhibit the tyrosine tRNA synthase of the parasite. With high potency, good oral bioavailability, and minimal host cell toxicity, these inhibitors show promise as next-generation antimalarials.
查看更多>>摘要：The SARS-CoV-2 Omicron variant has evolved into four sub-lineages-BA.1, BA.1.1, BA.2, and BA.3-with BA.2 becoming dominant worldwide. We and others have reported antibody evasion of BA.1 and BA.2, but side-by-side comparisons of Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are necessary. Using VSV-based pseudovirus, we report that sera from individuals vaccinated by two doses of an inactivated whole-virion vaccine shows weak to no neutralization activity, while homologous or heterologous boosters markedly improve neutralization titers against all Omicron sub-lineages. We also present neutralization profiles against a 20 mAb panel, including 10 authorized or approved, against the Omicron sub-lineages, along with mAb mapping against single or combinatorial spike mutations. Most mAbs lost neutralizing activity, while some demonstrate distinct neutralization patterns among Omicron sub-lineages, reflecting antigenic differences. Collectively, our results suggest the Omicron sub-lineages threaten the neutralization efficacy of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters.
查看更多>>摘要：Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis-retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anerobic bacteria significantly reduced retinol, atRA, and 13cisRA, whereas introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy.
Evans, John P.Zeng, CongQu, PankeFaraone, Julia...
13页
查看更多>>摘要：Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1 .1 , and BA.2, have reignited concern over potential escape from vaccine- and infection-induced immunity. We examine the sensitivity of these sub-lineages and other major variants to neutralizing antibodies from mRNA-vaccinated and boosted individuals, as well as recovered COVID-19 patients, including those infected with Omicron. We find that all Omicron sub-lineages, especially BA.1 and BA.1.1, exhibit substantial immune escape that is largely overcome by mRNA vaccine booster doses. While Omicron BA.1.1 escapes almost completely from neutralization by early-pandemic COVID-1 9 patient sera and to a lesser extent from sera of Delta-infected patients, BA.1.1 is sensitive to Omicron-infected patient sera. Critically, all Omicron sub-lineages, including BA.2, are comparably neutralized by Omicron patient sera. These results highlight the importance of booster vaccine doses for protection against all Omicron variants and provide insight into the immunity from natural infection against Omicron sub-lineages.
查看更多>>摘要：The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified-BA.1, BA.2, and BA.3-and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However, BA.2 was not efficiently neutralized by seven of eight antibodies used for COVID-19 therapy, including Sotrovimab, which robustly neutralized BA.1. In contrast, BA.2 and BA.3 (but not BA.1) were appreciably neutralized by Cilgavimab, which could constitute a treatment option. Finally, all sublineages were comparably and efficiently neutralized by antibodies induced by BNT162b2 booster vaccination after previous two-dose homologous or heterologous vaccination. Collectively, the Omicron sublineages show comparable cell entry and neutralization by vaccine-induced antibodies but differ in susceptibility to therapeutic antibodies.
Faria, Nuno R.Rambaut, AndrewPybus, Oliver G.Escalera-Zamudio, Marina...
15页
查看更多>>摘要：Although recombination is a feature of coronavirus evolution, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation thus far Here, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages to investigate the possibility of virus recombination among them. Our analyses reveal well-supported phylogenetic differences between the Orf1ab region encoding viral non-structural proteins and the rest of the genome, including Spike (5) protein and remaining reading frames. By accounting for several deletions in NSP6, Orf3a, and S, we conclude that the B.1.628 major cluster, now designated as lineage XB, originated from a recombination event between viruses of B.1.631 and B.1.634 lineages. This scenario is supported by the spatiotemporal distribution of these lineages across the USA and Mexico during 2021, suggesting that the recombination event originated in this geographical region. This event raises important questions regarding the role and potential effects of recombination on SARS-CoV-2 evolution.
查看更多>>摘要：Constitutive activation of plant immunity is detrimental to plant growth and development. Here, we uncover the role of a long non-coding RNA (lncRNA) in fine-tuning the balance of plant immunity and growth. We find that a lncRNA termed salicylic acid biogenesis controller 1 (SABC1) suppresses immunity and promotes growth in healthy plants. SABC1 recruits the polycomb repressive complex 2 to its neighboring gene NAC3, which encodes a NAC transcription factor. to decrease NAC3 transcription via H3K27me3. NAC3 activates the transcription of isochorismate synthase 1 (ICS1), a key enzyme catalyzing salicylic acid (SA) biosynthesis. SABC1 thus represses SA production and plant immunity via decreasing NAC3 and ICS/transcriptions. Upon pathogen infection, SABC1 is downregulated to derepress plant resistance to bacteria and viruses. Together, our findings reveal lncRNA SABC1 as a molecular switch in balancing plant defense and growth by modulating SA biosynthesis.
NSTL
Elsevier