Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-β1 (TGF-β1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-β1 (MsiTGF-β1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-β1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-β1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-β1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-β1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-β1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded positive-sense RNA virus, and the current strategies for controlling PRRSV are limited. Interferon gamma-inducible protein 16 (IFI16) has been reported to have a broader role in the regulation of the type I interferons (IFNs) response to RNA and DNA viruses. However, the function of IFI16 in PRRSV infection is unclear. Here, we revealed that IFI16 acts as a novel antiviral protein against PRRSV-2. IFI16 could be induced by interferon-beta (IFN-β). Overexpression of IFI16 could significantly suppress PRRSV-2 replication, and silencing the expression of endogenous IFI16 by small interfering RNAs led to the promotion of PRRSV-2 replication in MARC-145 cells. Additionally, IFI16 could promote mitochondrial antiviral signaling protein (MAVS)-mediated production of type I interferon and interact with MAVS. More importantly, IFI16 exerted anti-PRRSV effects in a MAVS-dependent manner. In conclusion, our data demonstrated that IFI16 has an inhibitory effect on PRRSV-2, and these findings contribute to understanding the role of cellular proteins in regulating PRRSV replication and may have implications for the future antiviral strategies.

The ASFV CD2V protein is a crucial antigen on the outer envelopes of virus particles. A modified ASFV CD2V dimeric protein was expressed in the Bac-to-Bac baculovirus expression vector system.