The ability of multimerized cyclophilin A to restrict retrovirus infection

Hassan Javanbakht, Felipe Diaz-Griffero, Wen Yuan, Darwin F. Yeung, Xing Li, Byeongwoon Song, Joseph Sodroski

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection.

Original languageEnglish (US)
Pages (from-to)19-29
Number of pages11
JournalVirology
Volume367
Issue number1
DOIs
StatePublished - Oct 10 2007
Externally publishedYes

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Keywords

  • Coiled-coil domain
  • Cyclophilin A
  • FIV
  • HIV-1
  • Multimerization
  • Restriction
  • Retroviral capsid
  • TRIM5
  • TRIMCyp

ASJC Scopus subject areas

  • Virology

Cite this

Javanbakht, H., Diaz-Griffero, F., Yuan, W., Yeung, D. F., Li, X., Song, B., & Sodroski, J. (2007). The ability of multimerized cyclophilin A to restrict retrovirus infection. Virology, 367(1), 19-29. https://doi.org/10.1016/j.virol.2007.04.034