Campbell EM. 2016. TRIM5α degradation via autophagy is not required for retroviral restriction

Sabrina Imam, Sarah Talley, Rachel S. Nelson, Adarsh Dharan, Christopher O'Connor, Thomas J. Hope, Edward M. Campbell*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

TRIM5α is an interferon-inducible retroviral restriction factor that prevents infection by inducing the abortive disassembly of capsid cores recognized by its C-terminal PRY/SPRY domain. The mechanism by which TRIM5α mediates the disassembly of viral cores is poorly understood. Previous studies demonstrated that proteasome inhibitors abrogate the ability of TRIM5α to induce premature core disassembly and prevent reverse transcription; however, viral infection is still inhibited, indicating that the proteasome is partially involved in the restriction process. Alternatively, we and others have observed that TRIM5α associates with proteins involved in autophagic degradation pathways, and one recent study found that autophagic degradation is required for the restriction of retroviruses by TRIM5α. Here, we show that TRIM5α is basally degraded via autophagy in the absence of restriction-sensitive virus. We observe that the autophagy markers LC3b and lysosome-associated membrane protein 2A (LAMP2A) localize to a subset of TRIM5α cytoplasmic bodies, and inhibition of lysosomal degradation with bafilomycin A1 increases this association. To test the requirement for macroautophagy in restriction, we examined the ability of TRIM5α to restrict retroviral infection in cells depleted of the autophagic mediators ATG5, Beclin1, and p62. In all cases, restriction of retroviruses by human TRIM5α, rhesus macaque TRIM5α, and owl monkey TRIM-Cyp remained potent in cells depleted of these autophagic effectors by small interfering RNA (siRNA) knockdown or clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing. Collectively, these results are consistent with observations that the turnover of TRIM5α proteins is sensitive to autophagy inhibition; however, the data presented here do not support observations that the inhibition of autophagy abrogates retroviral restriction by TRIM5 proteins.

Original languageEnglish (US)
Pages (from-to)3400-3410
Number of pages11
JournalJournal of virology
Volume90
Issue number7
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Imam, S., Talley, S., Nelson, R. S., Dharan, A., O'Connor, C., Hope, T. J., & Campbell, E. M. (2016). Campbell EM. 2016. TRIM5α degradation via autophagy is not required for retroviral restriction. Journal of virology, 90(7), 3400-3410. https://doi.org/10.1128/JVI.03033-15