Affiliation:
1. Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Hyderabad 500 076, India
Abstract
ABSTRACT
Lentiviruses, human immunodeficiency viruses (HIVs), and simian immunodeficiency
viruses (SIVs) are distinguished from oncoretroviruses by their ability
to infect nondividing cells such as macrophages. Retroviruses must gain
access to the host cell nucleus for replication and propagation. HIV
and SIV preintegration complexes (PIC) enter nuclei after traversing
the central aqueous channel of the limiting nuclear pore complex
without membrane breakdown. Among the nucleophilic proteins, namely,
matrix, integrase, Vpx, and Vpr, present in HIV type 2/SIV PIC, Vpx is
implicated in nuclear targeting and is also available for incorporation
into budding virions at the plasma membrane. The mechanisms of these
two opposite functions are not known. We demonstrate that Vpx is a
nucleocytoplasmic shuttling protein and contains two novel noncanonical
nuclear import signals and a leptomycin B-sensitive nuclear export
signal. In addition, Vpx interacts with the cellular tyrosine kinase
Fyn through its C-terminal proline-rich motif. Furthermore, our data
indicate that Fyn kinase phosphorylates Vpx and regulates its export
from nucleus. Replacement of conserved tryptophan residues within
domain 41 to 63 and tyrosine residues at positions 66, 69, and 71 in
Vpx impairs its nuclear export, virion incorporation, and SIV
replication in macrophages. Nuclear export is essential to ensure the
availability of Vpx in the cytoplasm for incorporation into virions,
leading to efficient viral replication within nondividing
cells.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
11 articles.
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