A gene polymorphism at SP-B 1580 site regulates the pulmonary surfactant tension of viral pneumonia through the cellular pyroptosis signaling pathway.

Background: Viral pneumonias, such as SARS and MERS, have been a recurrent challenge for the public healthcare system. COVID-19 posed an unprecedented global crisis. The primary impact of viral pneumonia is pathologic changes of lung tissue. However, the effect of SP-B site gene polymorphism on alveolar surface tension in viral pneumonia remains unexplored.

Objective: To explore the molecular mechanism of how the gene polymorphism at SP-B 1580 site regulates the pulmonary surfactant tension of viral pneumonia through the cellular pyroptosis signaling pathway using an animal experiment and a clinical trial.

Methods: We constructed a genetically modified mouse model of viral pneumonia and administered H5N1 influenza virus through intratracheal injection. After 48 hours, the survival rate of each mouse group was evaluated. Lung tissue, blood, and bronchoalveolar lavage fluid samples were collected for histopathologic analysis. Inflammatory factor concentrations were measured using ELISA. The level of apoptosis was determined using TUNEL assay. Changes in the expression of cell death-related factors were assessed using qRT-PCR and protein blotting. Additionally, blood samples from patients with viral pneumonia were analyzed to detect single nucleotide polymorphisms and explore their correlation with disease severity, inflammatory factor levels, and pulmonary surfactant protein expression.

Results: Following H5N1 infection of mice, the model group and hSP-B-C group showed high mortality rates within 24 hours. The survival rates in the blank control group, virus model group, hSP-B-C group, and hSP-B-T group were 100%, 50%, 37.5%, and 75%, respectively. Histologic analysis revealed significant lung tissue damage, congestion, alveolar destruction, and thickened alveolar septa in the model and hSP-B-C groups. However, these pulmonary lesions were significantly alleviated in the hSP-B-T group. Inflammatory factor levels were elevated in the model and hSP-B-C groups but reduced in the hSP-B-T group. TUNEL assay demonstrated a decrease in apoptotic cells in the lungs of the hSP-B-T group. Furthermore, the expression of SP-B and cell death-related proteins was downregulated in all three groups, with the lowest expression observed in the hSP-B-C group. The clinical trial found that patients with severe viral pneumonia exhibited a higher frequency of CC genotype and C allele in, along with increased inflammatory factor levels and decreased SP-B expression compared to those with mild-to-moderate viral pneumonia.

Conclusion: SP-B polymorphism at the 1580 site regulates lung surfactant tension through the cell pyroptosis signaling pathway, thus affecting the progression of viral pneumonia.