J Biol Chem. 2012 Mar 9;287(11):8457-67. doi: 10.1074/jbc.M111.312561. Epub 2012 Jan 17.
Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry.
Abstract
Phosphatidylinositol
kinases (PI kinases) play an important role in the life cycle of
several viruses after infection. Using gene knockdown technology, we
demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required
for cellular entry by pseudoviruses bearing the severe acute respiratory
syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry
mediated by SARS-CoV spike protein is strongly inhibited by knockdown of
PI4KB. Consistent with this observation, pharmacological inhibitors of
PI4KB blocked entry of SARS pseudovirions. Further research suggested
that PI4P plays an essential role in SARS-CoV spike-mediated entry,
which is regulated by the PI4P lipid microenvironment. We further
demonstrate that PI4KB does not affect virus entry at the SARS-CoV
S-ACE2 binding interface or at the stage of virus internalization but
rather at or before virus fusion. Taken together, these results indicate
a new function for PI4KB and suggest a new drug target for preventing
SARS-CoV infection.
- PMID:
- 22253445
- PMCID:
- PMC3318727
- DOI:
- 10.1074/jbc.M111.312561
Joitain PI4KIIIbeta inhibittoreita on olemassa.
https://www.sciencedirect.com/science/article/pii/S0960894X14007392?via%3Dihub
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