Fig. 1.

Two main pathways of virus-induced injury and pulmonary fibrosis. ① Viral infection causes direct damage to the lung. During most viral infections, the virus causes prompt and direct damage to the lung. Wound healing response is activated at this time, however, the virus induces persistent lung damage and/or abnormal wound-healing, leading to occurrence of pulmonary fibrosis. ② Viral infection causes immune-mediated injury. Virus infection activates the immune system. Macrophages, neutrophils, eosinophils, and Th2 cells aggregate at the site of injury and release a large number of pro-inflammatory and pro-fibrotic cytokines/factors such as TGF-β, TNF-α, MMPs, TIMPs, IL-1, IL-4, IL-5, IL-6, IL-13 and IL-17. The combination of the virus and these factors induces sustained and substantial lung damage, promoting pulmonary fibrosis