16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

HUMAN TRIPARTITE MOTIF PROTEIN 1 BLOCKS HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. WeAa0102

Marchant D.¹, Neil S.J.D.², Carter G.², Harrison I.², Aubin K.², Meroni G.³, McKnight Á.^2
1University of British Columbia, The James Hogg iCAPTURE centre, Vancouver, United Kingdom, ²Wohl Virion Centre, Windeyer Institute of Medical Sciences, UCL, London, United Kingdom, ³Telethon Institute of Genetics and Medicine, Naples, Italy

Rhesus Tripartite motif protein 5α (rhTRIM 5α) constitutes lentiviral restriction factor 1 (Lv1), which restricts HIV-1 in a cross species specific manner. Lv2 is a distinct restriction factor that protects human cells from infection by certain HIV-1 and HIV-2 strains. Similar to Lv1, Lv2 operates post-entry and targets the incoming viral CA. The human factors for Lv2 have not been previously determined. We investigated if human TRIMs could mediate Lv2 activity. We used siRNA to silence TRIM genes, western blotting and Retroviral expression constructs to make stable expressing cell lines. We identified huTRIM 1 as a blocking factor that constitutes Lv2. We show that a high level of TRIM 1 expression is limited to non-permissive cells and that down-modulation of its expression by siRNA overcomes the restriction in non-permissive cells, including monocyte derived macrophages. Permissive cells are rendered restrictive if made to express TRIM 1. After fusion with the cell membrane and entry into the cytoplasm, HIV-1 and -2 must therefore avoid host intracellular anti-viral factors including TRIM 1 to complete replication. It will be important to determine the role of these TRIM proteins in the tissue compartmentalisation and pathogenesis of HIV.

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2006-08-13
WeAa0102

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