Mechanism Of SARS Lung Damage Identified

The results offer up a new pathway to treat the pulmonary damage of SARS.

Infection with the SARS virus can lead to severe inflammation in the lungs, which can lead to respiratory distress, fibrosis, and eventually lung failure. Ye-Guang Chen and colleagues tested the effect of a SARS viral protein, the nucleocapsid protein (the protein that binds the virus's genetic material), on human lung cells and found that this protein can bind to a cellular protein called Smad3.

By associating with Smad3, the nucleocapsid protein accomplishes two things. First, it prevents Smad3 from binding to its partner Smad4 and initiating cell suicide, allowing the virus to replicate longer. At the same time, Smad3-Nucleocapsid binding stimulates a separate pathway that promotes the production of collagen and an inhibitor (PAI-1) of the plasminogen protein, which breaks down non-cell materials and other build-up in the body, leading to lung fibrosis.

So, in a trade-off, the SARS virus increases its short-term gain at the expense of long-term damage to its host.

This research was recently published in the Journal of Biological Chemistry. Corresponding Author: Ye-Guang Chen, Department of Biological Sciences and Biotechnology, Tsinghua University.