Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1.

Abstract

In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5alpha with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain.

• Authors: Felipe Diaz-Griffero, Nick Vandegraaff, Yuan Li, Kathleen McGee-Estrada, Matthew Stremlau, Sohanya Welikala, Zhihai Si, Alan Engelman, Joseph Sodroski
• Journal: Virology (Virology) Vol. 351 Issue 2 Pg. 404-19 (Aug 01 2006) ISSN: 0042-6822 [Print] United States
• PMID: 16650449 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Carrier Proteins
• Recombinant Fusion Proteins
• Cyclophilin A

Topics

• Animals
• Aotidae
• Capsid (metabolism)
• Carrier Proteins (genetics, metabolism)
• Cell Line
• Cyclophilin A (genetics, metabolism)
• Gene Expression Regulation
• HIV-1 (metabolism)
• Humans
• Mutation
• Protein Binding
• Recombinant Fusion Proteins (genetics, metabolism)
• Virus Replication