The host restriction factor SERINC5 inhibits HIV-1 transcription by negatively regulating NF-κB signaling

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Serine incorporator 5 (SER5) is known to inhibit HIV-1 entry.
• Recent studies suggest SER5 also impacts HIV-1 transcription and virion production.
• The precise mechanisms of SER5's anti-transcriptional activity against HIV-1 are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms by which SER5 inhibits HIV-1 transcription.
• To investigate the role of NF-κB signaling in SER5-mediated HIV-1 repression.

Main Methods:

• Investigated the interaction of SER5 with components of the NF-κB pathway.
• Utilized ubiquitination assays to examine the role of TRIM40.
• Assessed the impact of SER5 on MDA5 and RIG-I stability and nuclear translocation.
• Measured HIV-1 LTR-driven gene expression.

Main Results:

• SER5 inhibits HIV-1 transcription by negatively regulating NF-κB signaling.
• SER5 recruits TRIM40 to mediate K48-linked polyubiquitination and proteasomal degradation of MDA5 and RIG-I.
• This degradation impedes nuclear translocation of the p50/p65 dimer.
• SER5 represses HIV-1 LTR-driven gene expression.

Conclusions:

• SER5 restricts HIV-1 replication by inhibiting NF-κB-mediated viral gene expression.
• The findings reveal a novel mechanism of HIV-1 restriction involving SER5, TRIM40, MDA5, and RIG-I.
• SER5 represents a potential therapeutic target for controlling HIV-1 infection.