Hydroxylation of the HIV-1 antisense protein promotes immune evasion of HIV-1 via modulation of TBK1 - PubMed
3 hours ago
- #TBK1 modulation
- #ASP hydroxylation
- #HIV-1 immune evasion
- HIV-1 uses its antisense protein (ASP) to evade the host immune system by inhibiting the type I interferon response.
- The hydroxylation of ASP at Pro47 by host enzyme PHD3 leads to RNF114 recruitment, causing K6-linked ubiquitination of TBK1 at Lys236, which suppresses TBK1 activation and downstream immune signaling.
- Experimental interventions, such as ASP deletion or using inhibitors for RNF114 or PHD3, enhance antiviral immunity and reduce HIV-1 replication in humanized mice.
- Clinical data from treatment-naive patients show positive correlations between RNF114 and PHD3 transcript levels and HIV-1 viral load, underscoring their role in infection progression.