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TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling

Uchil, Pradeep D
Mothes, Walther
Published in Journal of Virology. 2015, vol. 90, no. 1, p. 308-316
Abstract Host restriction factor TRIM5 inhibits retroviral transduction in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. However, the restriction mechanism may not be that simple since TRIM5 E3 ubiquitin ligase activity, the proteasome, autophagy, and TAK1-dependent AP-1 signaling have been suggested to contribute to restriction. Here, we show that, among a panel of seven primate and Carnivora TRIM5 orthologues, each of which has potential for potent retroviral restriction activity, all activated AP-1 signaling. In contrast, TRIM family paralogues most closely related to TRIM5 did not. While each primate species has a single TRIM5 gene, mice have at least seven TRIM5 homologues that cluster into two groups, Trim12a, -b, and -c and Trim30a, -b, -c, and -d. The three Trim12 proteins activated innate immune signaling, while the Trim30 proteins did not, though none of the murine Trim5 homologues restricted any of a panel of cloned retroviruses. To determine if any mouse TRIM5 homologues had potential for restriction activity, each was fused to the human immunodeficiency virus type 1 (HIV-1) CA binding protein cyclophilin A (CypA). The three Trim12-CypA fusions all activated AP-1 and restricted HIV-1 transduction, whereas the Trim30-CypA fusions did neither. AP-1 activation and HIV-1 restriction by the Trim12-CypA fusions were inhibited by disruption of TAK1. Overall then, these experiments demonstrate that there is a strong correlation between TRIM5 retroviral restriction activity and the ability to activate TAK1-dependent innate immune signaling.
Keywords AnimalsCarrier Proteins/metabolismCatsCell LineHumansImmunity, InnateMiceRetroviridae/genetics/immunologySignal TransductionTranscription Factor AP-1/metabolismTransduction, Genetic
PMID: 26468522
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LASCANO MAILLARD, Maria Josefina et al. TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling. In: Journal of Virology, 2015, vol. 90, n° 1, p. 308-316. doi: 10.1128/JVI.02496-15 https://archive-ouverte.unige.ch/unige:92033

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Deposited on : 2017-02-22

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