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This article is part of the supplement: Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Open Access Invited speaker presentation

Retroviral restriction factors: new mechanisms of innate immunity

Daniel Wolf1, Guangxia Gao2, Xuemin Guo2, Matthew J Bick3, John-William N Carroll3, Margaret R MacDonald3 and Stephen P Goff1*

  • * Corresponding author: Stephen P Goff

Author Affiliations

1 Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY, USA

2 Center for Infections and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, PR China

3 Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY, USA

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Retrovirology 2009, 6(Suppl 2):I1 doi:10.1186/1742-4690-6-S2-I1

Published: 24 September 2009

First paragraph (this article has no abstract)

We are interested in characterizing the cellular machinery involved in the restriction of retrovirus replication - the components of the innate or ''intrinsic'' immunity. Studies of two such systems will be presented. In the first example, we have identified components involved in transcriptional silencing of proviral DNA by Embryonic Stem (ES) cells. It has long been known that ES cells potently block provirus expression via a transacting factor that binds to the primer binding site (PBS) for proline tRNA on the murine leukemia virus genome. We have purified the silencing complex and identified TRIM28 (Kap-1), a known transcriptional silencer, as an integral component of the complex. Further, we have identified the DNA sequence-specific binding component of the complex as being ZFP809, one of the dozens of zinc finger proteins encoded in the mammalian genome. We show that expression of ZFP809 is sufficient to render even differentiated cells highly resistant to MLV infection. Furthermore, we demonstrate that ZFP809 is able to potently block transcription from DNA constructs of human T-cell lymphotropic virus-1 (HTLV-1), which use the same primer tRNA. Finally, we found that similar silencing occurs at the distinct PBS for at least one other tRNA (namely, Lys1,2) utilized by such viruses as visna and spuma.