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Researchers discover new role for protein MMP-12 in antiviral immunity

Posted: 12 May, 2014

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In a recent publication in the prestigious journal, Nature Medicine, a team of researchers have discovered a new role for a white blood cell protein in anti-viral immunity.

The study, co-led by Drs. David Marchant, (University of Alberta), Bruce McManus (Providence Health Care and UBC), and Christopher Overall (UBC Department of Oral Biological and Medical Sciences), focused on a protein called MMP-12, one of several proteins in a family of proteins called matrix metalloproteinases. MMP-12 is known to play a role in “chewing up” other proteins outside of cells within tissues of different organs. However, the researchers discovered that MMP-12 also helps in protecting tissues against viral infection in models of human heart and lung infection. The common viruses that the MMP-12 was protective against are known as Coxsackievirus (which attacks the heart muscle and can cause heart failure) and respiratory syncytial virus (RSV), one of the greatest causes of hospitalization of infants.

During a viral infection, infected cells produce an important anti-viral protein called interferon-alpha. The study shows that MMP-12 promotes the anti-viral action of interferon-alpha by helping the release of this important immune molecule into tissues and organs where it suppresses virus infection. This role of MMP-12 in controlling the production and cellular release of interferon-alpha was previously unknown.

These findings are especially exciting because the antiviral function of MMP-12 points to a pivotal role of the protein in controlling a broad range of many different viruses. In addition, later in virus infection MMP-12 keeps the immune response in check by cutting interferon-alpha to pieces to prevent side effects from the immune response. The researchers used this facet of MMP-12 activity to develop a new drug that blocks MMP-12 activity outside the cell and raises the levels of antiviral interferon-alpha. This led to protection in mouse models of virus infection. These findings suggest that blocking MMP-12 levels or function may help improve the outcome of viral infections in humans. More research is needed to determine this, and to further the understanding of the function of MMP-12—potentially leading to new therapeutic advances to protect against and treat viral infections. The work also opens a whole new door of biology for the MMP family, suggesting that other immune functions may be altered by MMP actions, either in the nucleus of cells, in cell cytoplasm or outside of cells.

Find the full publication here.

The journal also featured a News and Views article related to the study. It can be found here.