cell biology / antiviral immune response · BEGINNER LESSON
RIPA
RIPA stands for RIG-I-like receptor-induced IRF3-mediated pathway of apoptosis. It is a virus-triggered cell-death pathway in which IRF3 helps infected cells undergo apoptosis, which limits viral spread.
What RIPA is and what is measured
RIPA is a pathway, not a molecule. It is part of the antiviral response in infected cells, and the key outcome is whether an infected cell enters apoptosis, meaning programmed cell death. In experiments, researchers measure IRF3 activation, IRF3 binding to BAX, cytochrome c release from mitochondria, caspase activation, and whether infected cells stop producing infectious virus particles.
[1] RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway
How the pathway works
RIPA begins when RIG-I-like receptors, or RLRs, detect viral infection and activate IRF3, a transcription factor, meaning a protein that can control gene activity. In the RIPA branch, IRF3 is modified by linear polyubiquitination, a chain-like addition of ubiquitin proteins. This activation is different from IRF3’s gene-control role. Activated IRF3 binds the pro-apoptotic protein BAX through a BH3 region near its C-terminus, or tail end. The IRF3-BAX complex moves to mitochondria, which are energy-producing structures in the cell, and this leads to cytochrome c release and then caspase activation, ending in apoptosis.
[1] RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway
Why it matters in infection
RIPA can reduce viral replication and disease in mice, and cells lacking RIPA can remain persistently infected and keep producing infectious virus even when interferon-beta, or IFN-β, and other antiviral genes are active. This shows that IRF3 has two antiviral roles: it can help turn on antiviral genes in the nucleus and it can also trigger cell death through RIPA. The relative importance of these two roles can vary by virus and cell type.
[1] RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway
Mechanistic details and limitations
The source says RIPA needs some shared IRF3 pathway components plus RIPA-specific ones such as TRAF2 and TRAF6. The activating ubiquitin modification is made by the LUBAC complex. A timing feature also matters: early after infection, the anti-apoptotic protein XIAP blocks caspase activation, and later XIAP is degraded so apoptosis can proceed. A limitation is that the exact contribution of RIPA versus IRF3’s transcriptional function is not identical in every infection context.
[1] RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway
SEE THE IDEA
RIPA pathway overview
RIG-I-like receptors detect infection and start the response.
IRF3 receives a linear ubiquitin modification made by LUBAC with help from TRAF2 and TRAF6.
Activated IRF3 binds BAX, the complex reaches mitochondria, and cytochrome c is released.
Caspases become active and the infected cell undergoes programmed cell death.
Detection leads to IRF3 activation, which leads to mitochondrial damage signaling, which leads to apoptosis.
RIPA is an antiviral branch that pushes infected cells toward self-destruction after IRF3 activation.
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Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.