Restriction Factors

To combat viral infections, the mammalian immune system has developed many defenses against it, some of which works against HIV and other retroviruses, targeting different aspects of their life cycle, restricting their replication. The following restriction factors are some of the most well-studied examples. 

APOBEC

APOBEC3G (A3G) is a protein that is produced by the host cell and is packaged into budding viruses. After these viruses infect a new host cell, A3G produces a large number of changes in the HIV genome, which causes the virus to become non-infectious due to catastrophic errors in its genetic sequence. This process is shown in the animation on the left.

Viral Infectivity Factor (Vif)

As shown in the animation above, HIV counteracts A3G restriction by encoding a protein called viral infectivity factor (Vif). Vif hijacks the host’s molecular machinery and uses it to destroy A3G, preventing A3G from being packaged into new HIV virions.

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TRIM5α

The tripartite-motif protein (TRIM5) proteins are restriction factors that block retroviral infections by binding to viral capsids soon after entry into the host cell and preventing reverse transcription.

 TRIM5 is a mammalian restriction factor that can potently block viral replication. It is part of the innate immune system. TRIM5α (colored purple) can bind to the HIV capsid shell (yellow) that coats and protects the viral genome. Structural studies have shown that TRIM5 can form a cage-like structure surrounding the capsid. There are three proposed mechanisms by which TRIM5 can inhibit HIV infection: 1) causing premature uncoating of the viral capsid, 2) recruiting ubiquitin, which leads to non-productive uncoating of the virus, 3) virophagy in which the TRIM5 cage directs the viral capsid to get degraded by digested enzymes contained in a membrane structure called lysosome.

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