Molecular functions of HAX1 during disease progress.

HCLS1-associated protein X-1 (HAX1) is a newly discovered multifunctional cell regulatory protein that is widely expressed in cells and has a close relationship with multiple cellular proteins. HAX1 plays important roles in various processes, including the regulation of apoptosis, maintenance of mitochondrial membrane potential stability and calcium homeostasis, occurrence and development of diseases, post-transcriptional regulation of gene expression, and host immune response after viral infection. In this article, we have reviewed the research progress on the biological functions of HAX1, thereby laying a theoretical foundation for further exploration of its underlying mechanisms and targeted application.

ASFV infection induces macrophage necroptosis and releases proinflammatory cytokine by ZBP1-RIPK3-MLKL necrosome activation.

African swine fever (ASF) is an infectious disease characterized by hemorrhagic fever, which is highly pathogenic and causes severe mortality in domestic pigs. It is caused by the African swine fever virus (ASFV). ASFV is a large DNA virus and primarily infects porcine monocyte macrophages. The interaction between ASFV and host macrophages is the major reason for gross pathological lesions caused by ASFV. Necroptosis is an inflammatory programmed cell death and plays an important immune role during virus infection. However, whether and how ASFV induces macrophage necroptosis and the effect of necroptosis signaling on host immunity and ASFV infection remains unknown. This study uncovered that ASFV infection activates the necroptosis signaling in vivo and macrophage necroptosis in vitro. Further evidence showed that ASFV infection upregulates the expression of ZBP1 and RIPK3 to consist of the ZBP1-RIPK3-MLKL necrosome and further activates macrophage necroptosis. Subsequently, multiple Z-DNA sequences were predicted to be present in the ASFV genome. The Z-DNA signals were further confirmed to be present and colocalized with ZBP1 in the cytoplasm and nucleus of ASFV-infected cells. Moreover, ZBP1-mediated macrophage necroptosis provoked the extracellular release of proinflammatory cytokines, including TNF-α and IL-1ß induced by ASFV infection. Finally, we demonstrated that ZBP1-mediated necroptosis signaling inhibits ASFV replication in host macrophages. Our findings uncovered a novel mechanism by which ASFV induces macrophage necroptosis by facilitating Z-DNA accumulation and ZBP1 necrosome assembly, providing significant insights into the pathogenesis of ASFV infection.

Annexin A2: A Double-Edged Sword in Pathogen Infection.

Annexin A2 (ANXA2) is a multifunctional calcium- and phospholipid-binding protein that plays an important role in various cells. During pathogen infections, ANXA2 modulates the nuclear factor kappa-B (NF-κB) and cell apoptosis signaling pathways and guides the chemotaxis of inflammatory cells toward inflammation sites, thereby protecting the host organism through the modulation of the inflammatory response. In addition, ANXA2 can regulate immune responses, and in certain pathogen infections, it can interact with pathogen proteins to facilitate their invasion and proliferation. This review provides an overview of the research progress on how ANXA2 regulates pathogen infections.

Identification and verification of the role of key metabolites and metabolic pathways on ASFV replication.

African swine fever virus (ASFV) infection usually causes viremia within a few days. However, the metabolic changes in pig serum after ASFV infection remain unclear. In this study, serum samples collected from ASFV-infected pigs at different times were analyzed using pseudotargeted metabolomics method. Metabolomic analysis revealed the dopaminergic synapse pathway has the highest rich factor in both ASFV5 and ASFV10 groups. By disrupting the dopamine synaptic pathway, dopamine receptor antagonists inhibited ASFV replication and L-dopa promoted ASFV replication. In addition, guanosine, one of the top20 changed metabolites in both ASFV5 and ASFV10 groups suppressed the replication of ASFV. Taken together, this study revealed the changed serum metabolite profiles of ASFV-infected pigs at various times after infection and verified the effect of the changed metabolites and metabolic pathways on ASFV replication. These findings may contribute to understanding the pathogenic mechanisms of ASFV and the development of target drugs to control ASF.