What is it about?

DDX3X is a protein in the human body that controls various important functions including immunity. To do this, DDX3X enters and exits the nucleus and controls cells at the DNA/RNA level. However, because most human viruses carry very little information themselves, they often manipulate proteins such as DDX3X to control many cellular functions at once. This includes HIV, which has claimed over 38 million lives and still has no known cure. Until now, why DDX3X enters the nucleus, what effect this has on gene activity, and how it exits again, were unclear.

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Why is it important?

Our work reveals that DDX3X enters the nucleus upon exposure to viral RNA. There, it supports antiviral immunity in part by altering the activity of dozens of genes. We also show how DDX3X exits the nucleus again, a process which is controlled by the HIV virus and is essential for its replication. We may now create entirely new anti-HIV drugs armed with this new understanding. Our work may also have important implications in autoimmunity and cancer.


Given the likely limits on future economic output due to the changing demographics of our society, I believe it is essential that we urgently develop treatments that break through the ‘impossible triangle’ of cost, effectiveness, and robustness against mutant strains. Our revised model of DDX3X's subcellular trafficking will support efforts towards host-oriented therapies that overcome these challenges.

Dr. Steven Heaton
RIKEN Center for Integrative Medical Sciences

Read the Original

This page is a summary of: Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX3X is Central to its Role in Antiviral Immunity, Cells, September 2019, MDPI AG,
DOI: 10.3390/cells8101181.
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