Aggravated effects of human parvovirus B19 NS1 protein on bleomycin‑induced pulmonary fibrosis.

Abstract

Interstitial lung diseases (ILDs) include various lung parenchymal disorders characterized by inflammation and fibrosis of the lung tissue, leading to progressive dyspnea and respiratory failure. Clinical evidence has suggested an association between human parvovirus B19 (B19V) infection and the progression of ILD and pulmonary fibrosis, but the mechanisms involved remain unclear. The present study screened 86 patients with connective tissue disease (CTD) and reported that B19V infection was significantly more prevalent among those with ILD than among those without (P<0.001). To investigate the potential underlying mechanisms, a bleomycin (BLM)&#x2011;treated mouse model was employed to assess the effect of B19V nonstructural protein 1 (NS1) on pulmonary fibrosis. Mice treated with BLM or BLM + NS1 exhibited markedly higher fibrosis scores, hydroxyproline content, and higher levels of transforming growth factor&#x2011;&#x3b2; and collagen I. Treatment with nintedanib attenuated fibrosis in both groups; however, lung fibrosis remained more pronounced in the BLM + NS1 group than in the BLM group. Furthermore, the levels of neutrophil&#x2011;associated markers, including citrullinated histone H3 and myeloperoxidase, as well as inflammasome&#x2011;related factors, such as IL&#x2011;18 and IL&#x2011;17A, were markedly elevated in lung tissues from both groups, with the highest levels observed in the BLM + NS1 group. These findings suggested that B19&#x2011;NS1 may exacerbate fibrosis in patients with ILD by increasing neutrophil&#x2011;driven responses and inflammasome activation, highlighting a need for nintedanib therapies to more effectively address B19V&#x2011;associated pulmonary fibrosis.