Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I.

Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, the impact of the virus on glucose metabolism in host cells and the subsequent effects are still unknown. Here, glycolysis induced by SVA is shown to facilitate virus replication by promoting lactate production, which then attenuates the interaction between the mitochondrial antiviral-signaling protein (MAVS) and retinoic acid-inducible gene I (RIG-I). SVA induces glycolysis in PK-15 cells, as indicated by significantly increased expression of hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate kinase 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), and superoxide dismutase-2 (SOD2) in a dose-and replication-dependent manner, and enhanced lactate production, while reducing ATP generation. Overexpression of PKM, PGK1, HIF-1α, and PDK3 in PK-15 cells and high glucose concentrations promote SVA replication, while glycolytic inhibitors decrease it. Inhibition of RLR signaling allowed better replication of SVA by promoting lactate production to attenuate the interaction between MAVS and RIG-I, and regulatory effect of glycolysis on replication of SVA was mainly via RIG-I signaling. SVA infection in mice increased expression of PKM and PGK1 in tissues and serum yields of lactate. Mice treated with high glucose and administered sodium lactate showed elevated lactate levels and better SVA replication, as well as suppressed induction of RIG-I, interferon beta (IFNß), IFNα, interferon-stimulated gene 15 (ISG15), and interleukin 6 (IL-6). The inhibitory effect on interferons was lower in mice administered sodium oxamate and low glucose compared to the high glucose, indicating that RLR signaling was inhibited by SVA infection through lactate in vitro and in vivo. These results provide a new perspective on the relationship between metabolism and innate immunity of the host in SVA infection, suggesting that glycolysis or lactate may be new targets against the virus.

Suppressor of cytokine signaling 1 (SOCS1) inhibits antiviral responses to facilitate Senecavirus A infection by regulating the NF-κB signaling pathway.

Senecavirus A (SVA) is a new virus inducing porcine idiopathic vesicular disease that causes significant economic losses. Although some progress has been made in etiological research, the role of host factors in SVA infection remains unclear. This study investigated the role of the host factor, suppressor of cytokine signaling 1 (SOCS1), in SVA infection. The expression of SOCS1 was significantly upregulated with infection of SVA in a dose-dependent manner, and SOCS1 inhibited the expression of type I interferons (IFN-α, IFN-ß) and the production of interferon stimulating genes (ISGs) (ISG56, ISG54, PKR), thereby facilitating viral replication. Further results showed that inhibition of antiviral responses of SOCS1 was achieved by regulating the NF-κB signaling pathway, which attenuates the production of IFNs and pro-inflammatory cytokines. These findings provide a new perspective of SVA pathogenesis and may partially explain the persistence of this infection. Moreover, the data indicate that targeting SOCS1 can help in developing new agents against SVA infection.

Cloning of long sterile lemma (lsl2), a single recessive gene that regulates spike germination in rice (Oryza sativa L.).

BACKGROUND: Rice is a typical monocotyledonous plant and an important cereal crop. The structural units of rice flowers are spikelets and florets, and floral organ development and spike germination affect rice reproduction and yield. RESULTS: In this study, we identified a novel long sterile lemma (lsl2) mutant from an EMS population. First, we mapped the lsl2 gene between the markers Indel7-22 and Indel7-27, which encompasses a 25-kb region. The rice genome annotation indicated the presence of four candidate genes in this region. Through gene prediction and cDNA sequencing, we confirmed that the target gene in the lsl2 mutant is allelic to LONG STERILE LEMMA1 (G1)/ELONGATED EMPTY GLUME (ELE), hereafter referred to as lsl2. Further analysis of the lsl2 and LSL2 proteins showed a one-amino-acid change, namely, the mutation of serine (Ser) 79 to proline (Pro) in lsl2 compared with LSL2, and this mutation might change the function of the protein. Knockout experiments showed that the lsl2 gene is responsible for the long sterile lemma phenotype. The lsl2 gene might reduce the damage induced by spike germination by decreasing the seed germination rate, but other agronomic traits of rice were not changed in the lsl2 mutant. Taken together, our results demonstrate that the lsl2 gene will have specific application prospects in future rice breeding. CONCLUSIONS: The lsl2 gene is responsible for the long sterile lemma phenotype and might reduce the damage induced by spike germination by decreasing the seed germination rate.