Matrix metalloproteinase 3 restricts viral infection by enhancing host antiviral immunity.

Viral pandemics pose great threats to human health and the economy. The host evolved a complex immune response against viral infection. Matrix metalloproteinase 3 (MMP3), also known as stromelysin-1, has an emerging role in immune regulation during pathogen infection. Using in vitro and in vivo infection models, we showed that MMP3 exhibits broad-spectrum antiviral activities against vesicular stomatitis virus (VSV), influenza A virus (H1N1) and human herpes virus 1 (HSV-1). MMP3 deficient mice are susceptible to viral infection and display a compromised antiviral immune response. Correspondingly, the mice with MMP3 overexpression are resistant to viral infection. The mechanistic study suggested that MMP3 is translocated from the cytoplasm into the cell nucleus upon virus infection and influence NF-κB activities, thus amplifying antiviral immune responses. This study suggested a novel function of MMP3 in viral infection and provided new ideas for developing antiviral drugs based on modulating MMP activity.