Abstract
Innate immunity conferred by the type I interferon is critical for antiviral defense. To date only a limited number of tripartite motif (TRIM) proteins have been implicated in modulation of innate immunity and anti-microbial activity. Here we report the complementary DNA cloning and systematic analysis of all known 75 human TRIMs. We demonstrate that roughly half of the 75 TRIM-family members enhanced the innate immune response and that they do this at multiple levels in signaling pathways. Moreover, messenger RNA levels and localization of most of these TRIMs were found to be altered during viral infection, suggesting that their regulatory activities are highly controlled at both pre- and posttranscriptional levels. Taken together, our data demonstrate a very considerable dedication of this large protein family to the positive regulation of the antiviral response, which supports the notion that this family of proteins evolved as a component of innate immunity.
| Original language | English |
|---|---|
| Pages (from-to) | 384-398 |
| Number of pages | 15 |
| Journal | Immunity |
| Volume | 38 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 21 Feb 2013 |
Bibliographical note
Funding Information:This research is partially supported by NIAID grants U54 AI57158 (North East Biodefense Center) (to A.G.-S.), R01DA033733 (to A.G.-S.), U19AI83025, (to A.G.-S. and J.J.), and P01AI090935 (to A.G.-S. and A.F.-S.). We thank J. Ayllon for kindly providing the ISG54 ISRE-luciferase reporter plasmid and D. Littman for providing plasmid pSIV3+. We thank A. Ballabio, P. Bieniasz, and F. Naya for kindly providing the TRIM expression plasmids specified in the supplemental information. We are grateful to M. Ooms for technical assistance related to lentivirus production and to R. Cadagan and O. Lizardo for technical support.
