A systematic regulatory network related to bulbil formation in Lilium lancifolium based on metabolome and transcriptome analyses.

BACKGROUND: Lilium lancifolium is a special wild triploid species native to China and can produce abundant bulbils on its stem under natural conditions, which is very valuable to study bulbil organogenesis in plants. Although similar to the lateral and tillering principles, the molecular mechanism underlying bulbil formation has remained incompletely understood. RESULTS: The metabolome and transcriptome of L. lancifolium bulbils across four development stages were analyzed. The pairwise comparison of metabolomes across the four stages identified 17 differential hormones, predominantly auxin (IAA), cytokinin (CK), and jasmonic acid (JA). Short Time-series Expression Miner (STEM) trend analysis of differential genes revealed four significant trends across these stages. The KEGG enrichment analysis of the four clusters highlighted pathways, such as plant hormone signal transduction, which were speculated to play a crucial role in development stages. these pathways were speculated to play a crucial role in development stages. To explore the key differential expressed genes and transcription factors associated with bulbil occurrence, two periods were focused on: Ll_UN and Ll_DN, which represented the stages with and without bulbils, respectively. Through correlation analysis and qRT-PCR analysis, 11 candidate differentially expressed genes and 27 candidate transcription factors were selected. By spraying exogenous hormones to validate these candidates, LlbHLH128, LlTIFY10A, LlbHLH93, and LlMYB108, were identified as the key genes for L. lancifolium bulbils. CONCLUSION: A regulatory network of L. lancifolium bulbil development was predicted. LlTIFY10A and LlbHLH93 might be involved in the JA and auxin signal transduction pathways, which jointly formed a regulatory network to affect the occurrence of L. lancifolium bulbil. This study not only provided more information about the differentially expressed genes and metabolites through transcriptome and metabolomics analyses, but also provided a clearer understanding of the effect of hormones on bulbil formation in lily.

Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection.

The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells' self-nucleic acids can be employed as a "danger signal" to alarm the immune system.

Activation and evasion of type I interferon responses by SARS-CoV-2.

The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-ß promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-ß treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.