TRIM5α degradation via autophagy is not required for retroviral restriction

摘要: UNLABELLED TRIM5α is an interferon-inducible retroviral restriction factor that prevents infection by inducing the abortive disassembly of capsid cores recognized its C-terminal PRY/SPRY domain. The mechanism which mediates viral poorly understood. Previous studies demonstrated proteasome inhibitors abrogate ability to induce premature core and prevent reverse transcription; however, still inhibited, indicating partially involved in process. Alternatively, we others have observed associates with proteins autophagic degradation pathways, one recent study found required for retroviruses TRIM5α. Here, show basally degraded via autophagy absence restriction-sensitive virus. We observe markers LC3b lysosome-associated membrane protein 2A (LAMP2A) localize a subset cytoplasmic bodies, inhibition lysosomal bafilomycin A1 increases this association. To test requirement macroautophagy restriction, examined restrict cells depleted mediators ATG5, Beclin1, p62. In all cases, human TRIM5α, rhesus macaque owl monkey TRIM-Cyp remained potent these effectors small interfering RNA (siRNA) knockdown or clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing. Collectively, results are consistent observations turnover sensitive inhibition; data presented here do not support abrogates TRIM5 proteins. IMPORTANCE Restriction factors class inhibit replication. Following fusion retrovirus host cell membrane, released into cytoplasm target cell. inhibits promoting incoming cores; as result, unable traffic nucleus, life cycle extinguished. process itself proteasome. However, present study, shown virus, both proteasomal pathways. Notably, does require machinery. These indicate effector functions can be separated from may further implications understanding mechanisms other TRIM family members.