Human DEAD-box protein 3 has multiple functions in gene regulation and cell
cycle control and is a prime target for viral manipulation.
Biochemical Pharmacology, 79 (3).
The human DEAD-box RNA helicase DDX3 has been implicated to play a role in the whole repertoire of
processes regulating gene expression, including transcription, splicing, mRNA export and translation. It
has also been suggested to be involved in cell cycle control and the regulation of apoptosis. In addition,
DDX3 was recently shown to be part of innate immune signalling pathways and to contribute to the
induction of anti-viral mediators, such as type I interferon. Interestingly, DDX3 appears to be a prime
target for viral manipulation: at least four different viruses, namely Hepatitis C virus (HCV), Hepatitis B
virus (HBV), Human Immunodeficiency Virus (HIV) and poxviruses, encode proteins that interact with
DDX3 andmodulate its function. HIV and HCV seem to co-opt DDX3 and require it for their replication. It
has therefore been suggested that DDX3 could be a novel target for the development of drugs against
these two viruses, both of which still pose major global health threats. However, in the light of the
apparent multifunctionality of DDX3 in the cell, drug development strategies targeting DDX3 will have
to be carefully evaluated. This review summarises the available data on the cellular functions of DDX3
and discusses theirmanipulation by the different viruses known to target DDX3. Understanding the viral
strategies for manipulating or co-opting DDX3 in functional and molecular detail can provide valuable
insights for the development of strategies to therapeutically target DDX3.
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