General model for retroviral capsid pattern recognition by TRIM5 proteins

Jonathan M. Wagner, Devin E. Christensen, Akash Bhattacharya, Daria M. Dawidziak, Marcin D. Roganowicz, Yueping Wan, Ruth A. Pumroy, Borries Demeler, Dmitri N. Ivanov, Barbie K. Ganser-Pornillos, Wesley I. Sundquist, Owen Pornillos

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity (KD of > 1 mM) and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher affinity (KD of ~10 μM) for isolated capsid subunits. Therefore, it has been argued that TRIMCyp proteins have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5α, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition.

Original languageEnglish (US)
Article numbere01563-17
JournalJournal of virology
Volume92
Issue number4
DOIs
StatePublished - Feb 1 2018

Keywords

  • Pattern recognition
  • Restriction factor
  • Retrovirus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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