Evolutionary constraints acting on DDX3X protein potentially interferes with Rev-mediated nuclear export of HIV-1 RNA

Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction of HIV-1 Rev, Exportin-1 (CRM-1) and DDX3X. Knock down of DDX3X has been shown to drastically impair...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2010-03, Vol.5 (3), p.e9613-e9613
Main Authors: Sharma, Deepak, Bhattacharya, Jayanta
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Active Transport, Cell Nucleus
Adenosine triphosphatase
Adenosine Triphosphatases - metabolism
AIDS
Algorithms
Amino acids
Animals
ATPases
Binding Sites
Computational Biology - methods
Computational Biology/Evolutionary Modeling
Computer applications
Computer Simulation
Customer relationship management software
Cytoplasm
Datasets
DEAD-box RNA Helicases - genetics
DNA helicase
Docking
Drosophila
Evolution, Molecular
Evolutionary Biology
Exports
Gene expression
Gene Products, rev - genetics
HIV
HIV-1 - genetics
Host-pathogen interactions
Human immunodeficiency virus
Humans
Insects
Ligands
Likelihood Functions
Logos
Medical research
Methods
Nuclear transport
Phylogenetics
Polypeptides
Protein Binding
Proteins
Replication
Residues
Ribonucleic acid
RNA
RNA helicase
RNA Helicases - metabolism
RNA transport
Simulation
Virology
Virology/Immunodeficiency Viruses
Virus replication
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction of HIV-1 Rev, Exportin-1 (CRM-1) and DDX3X. Knock down of DDX3X has been shown to drastically impair HIV replication. Here we show that evolutionary forces are responsible for demarking previously unidentified critical functionally important residues on the surface of DDX3X. Using computational approaches, we show that these functional residues, depending on their location, are capable of regulating ATPase and RNA helicase functions of DDX3X. The potential of these residues in designing better blockers against HIV-1 replication was also assessed. Also, using stepwise docking simulations, we could identify DDX3X-CRM-1 interface and its critical functional residues. Our data would help explain the role of DDX3X in HIV-1 Rev function with potential to design new intervention strategies against HIV-1 replication.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0009613