TRIM29 binds to and colocalizes with NEMO in the lysosome.
Houston Methodist researchers kept mice from getting the flu by removing a gene that regulates their immune system. According to a study recently published in Nature Immunology, mice missing the gene Trim29 eliminated human influenza virus within 48 hours, protecting them from infection.
“Influenza is the leading cause of death from infections worldwide. An effective treatment is vital, especially for children, the elderly and patients with compromised immune systems,” said Zhiqiang Zhang, Ph.D. “Mice lacking Trim29 kept them from a full blown infection and completely cleared them of the virus. This finding points the way to a potential flu treatment.”
Immune cells around the lungs are the first line of defense against infections. The gene Trim29, or Tripartite Interaction Motif 29, controls activation of lung immune cells after viral infections. Zhang’s team infected mice without the gene with the H1N1 flu virus and compared their survival and amount of virus to normal mice. Mice lacking Trim29 survived with no detectable infection or virus.
MOA: TRIM29 inhibited interferon-regulatory factors and signaling via the transcription factor NF-κB by degrading the adaptor NEMO. TRIM29 directly bound NEMO and subsequently induced its ubiquitination and proteolytic degradation. These data identify TRIM29 as a key negative regulator of alveolar macrophages and might have important clinical implications for local immunity and immunopathology. http://www.houstonmethodist.org/1285_houstonmethodist/1315_newsroom/1316_newsroom_newsandevents/newsdetail/?key=%7B09f1b536424148d7ac6b59543b6785f9%7D http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.3580.html
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