Abstract
| Original language | English |
|---|---|
| Article number | 1181 |
| Number of pages | 22 |
| Journal | Cells |
| Volume | 8 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 30 Sep 2019 |
Keywords
- DDX3X
- nuclear export
- exportin-1
- CRM1
- NES
- antiviral immunity
- parainfluenza virus
- HIV
- helicases
Cite this
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Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX3X is Central to its Role in Antiviral Immunity. / Heaton, Steven M.; Atkinson, Sarah C.; Sweeney, Melissa N.; Yang, Sundy N. Y.; Jans, David A.; Borg, Natalie A.
In: Cells, Vol. 8, No. 10, 1181, 30.09.2019.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX3X is Central to its Role in Antiviral Immunity
AU - Heaton, Steven M.
AU - Atkinson, Sarah C.
AU - Sweeney, Melissa N.
AU - Yang, Sundy N. Y.
AU - Jans, David A.
AU - Borg, Natalie A.
PY - 2019/9/30
Y1 - 2019/9/30
N2 - DEAD-box helicase 3, X-linked (DDX3X) regulates the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated antiviral response, but can also be a host factor contributing to the replication of viruses of significance to human health, such as human immunodeficiency virus type 1 (HIV-1). These roles are mediated in part through its ability to actively shuttle between the nucleus and the cytoplasm to modulate gene expression, although the trafficking mechanisms, and impact thereof on immune signaling and viral infection, are incompletely defined. We confirm that DDX3X nuclear export is mediated by the nuclear transporter exportin-1/CRM1, dependent on an N-terminal, leucine-rich nuclear export signal (NES) and the monomeric guanine nucleotide binding protein Ran in activated GTP-bound form. Transcriptome profiling and ELISA show that exportin-1-dependent export of DDX3X to the cytoplasm strongly impacts IFN-β production and the upregulation of immune genes in response to infection. That this is key to DDX3X's antiviral role was indicated by enhanced infection by human parainfluenza virus-3 (hPIV-3)/elevated virus production when the DDX3X NES was inactivated. Our results highlight a link between nucleocytoplasmic distribution of DDX3X and its role in antiviral immunity, with strong relevance to hPIV-3, as well as other viruses such as HIV-1.
AB - DEAD-box helicase 3, X-linked (DDX3X) regulates the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated antiviral response, but can also be a host factor contributing to the replication of viruses of significance to human health, such as human immunodeficiency virus type 1 (HIV-1). These roles are mediated in part through its ability to actively shuttle between the nucleus and the cytoplasm to modulate gene expression, although the trafficking mechanisms, and impact thereof on immune signaling and viral infection, are incompletely defined. We confirm that DDX3X nuclear export is mediated by the nuclear transporter exportin-1/CRM1, dependent on an N-terminal, leucine-rich nuclear export signal (NES) and the monomeric guanine nucleotide binding protein Ran in activated GTP-bound form. Transcriptome profiling and ELISA show that exportin-1-dependent export of DDX3X to the cytoplasm strongly impacts IFN-β production and the upregulation of immune genes in response to infection. That this is key to DDX3X's antiviral role was indicated by enhanced infection by human parainfluenza virus-3 (hPIV-3)/elevated virus production when the DDX3X NES was inactivated. Our results highlight a link between nucleocytoplasmic distribution of DDX3X and its role in antiviral immunity, with strong relevance to hPIV-3, as well as other viruses such as HIV-1.
KW - DDX3X
KW - nuclear export
KW - exportin-1
KW - CRM1
KW - NES
KW - antiviral immunity
KW - parainfluenza virus
KW - HIV
KW - helicases
U2 - 10.3390/cells8101181
DO - 10.3390/cells8101181
M3 - Article
VL - 8
JO - Cells
JF - Cells
SN - 2073-4409
IS - 10
M1 - 1181
ER -