Bovine respiratory syncytial virus (BRSV) is an enveloped RNA virus that utilizes clathrin-mediated endocytosis for cell entry and is a significant pathogen in bovine respiratory disease (BRD). Heat shock protein family A member 4 (HSPA4), a member of the HSP70 family, is known to be involved in the progression of various cancers. However, its role in virus entry has not been previously explored. Through experiments involving Western blot analysis, virus titer, and virus copies analysis, we demonstrated that HSPA4 can regulate BRSV entry and replication. The specific regulation mode is to enhance BRSV entry by promoting clathrin-mediated endocytosis. We used Western blot, virus titer, virus copies analysis, and IFA to demonstrate that HSPA4 can promote clathrin heavy chain protein (CHC) expression and further promote BRSV entry by activating the PI3K–Akt signaling pathway. Furthermore, we observed that HSPA4 boosts the efficiency of clathrin-mediated endocytosis by increasing the ATPase activity of heat shock cognate protein 70 (HSC70), thereby facilitating BRSV entry. Additionally, our investigation into the impact of HSPA4 on the entry of other viruses revealed that HSPA4 can facilitate the entry of a variety of viruses into host cells.

Excessive adipose tissue accumulation in sheep disrupts insulin signaling, inducing insulin resistance, and alters energy partitioning mechanisms. These changes adversely affect both ovine health and production efficiency. This study employed whole-genome resequencing to conduct selection signal analysis in long-fat-tailed (Lanzhou fat-tailed sheep) and short-fat-tailed (Hu sheep) breeds, investigating the genetic basis underlying divergent lipid metabolism-related traits between these distinct tail phenotypes. Fifteen healthy adult individuals, each from long-fat-tailed (Lanzhou Large-tailed sheep) and short-fat-tailed (Hu sheep) breeds, underwent whole-genome resequencing. Whole-genome resequencing analyses via F_ST, XP-CLR, and XP-EHH identified 75 significantly selected regions (p < 0.01), revealing eight key candidate genes (DAB1, DPP10, EPHA6, GPC5, KLF12, PAK7, PTPN3, TENM3). Subsequent functional enrichment analysis demonstrated significant enrichment of DAB1 and GPC5 in lipid metabolic processes (GO:0006629). Employing whole-genome resequencing-based selection signal analysis in long-fat-tailed (Lanzhou Large-tailed sheep) and short-fat-tailed (Hu sheep) breeds, this study identified two key lipid metabolism-associated genes (DAB1 and GPC5). These findings provide critical insights for conserving genetic resources and informing molecular breeding strategies targeting divergent tail phenotypes.

Encephalomyocarditis virus (EMCV) belongs to the genus Cardiovirus of the family Picornaviridae. It is a non-enveloped, positive-sense, single-stranded RNA virus and an important pathogen causing encephalomyocarditis (EMC). Tripartite motif 13 (TRIM13) is a member of the tripartite motif (TRIM) family and serves as an important effector molecule in antiviral innate immunity. However, its antiviral activity and underlying molecular mechanisms during EMCV infection remain unknown. In this study, we identified TRIM13 as a regulator of NF-κB activation. TRIM13, dependent on its E3 ubiquitin ligase activity, directly binds to IκBα and dose-dependently increases its phosphorylation level. To determine the chain type of IκBα polyubiquitination, antibodies specific for K48-linked and K63-linked ubiquitin were used. Our data indicated that IκBα was subjected to polyubiquitination independent of K48 and K63 linkages. This interaction promotes non-K48/K63-linked polyubiquitination of IκBα, thereby inducing NF-κB nuclear translocation. Subsequently, nuclear NF-κB activates the secretion of pro-inflammatory cytokines, exacerbating inflammatory responses and ultimately facilitating EMCV infection.