Viral interior design
How viruses rewire their hosts
to generate organelle platforms
for replication—and why that
might be their undoing
News from
F
or visitors who turn up with so
little, viruses have a nasty way
of making themselves at home
in their host. A virus arrives with
only its own RNA or DNA encased
in a protein and/or lipid coat that
protects its precious genetic material. Once inside the infected host,
the virus quickly uncoats, releasing
its genetic load, and starts smashing
up the cellular furniture to serve its
own reproductive needs. Viruses are
In uninfected human cells (A, C), the PI4P (red) and cholesterol
(green) are found colocalized at the Golgi apparatus (C, arrow,
particularly fond of assembling their
yellow). After infection with Coxsackievirus, a pathogenic RNA
replication machinery on the surface
virus (B, D), cellular membranes are remodeled dramatically to
of membrane-bound cellular organgenerate new so called “Replication organelles”, which are highly
elles such as the Golgi apparatus or
enriched in both PI4P and cholesterol (D, yellow). The virus uses
the mitochondria. It’s like home
these replication organelle membranes as platforms on which to
replicate. The PI4P and cholesterol were detected with live-cell
invasion bandits setting up a crystal
fluorescent reporters.
meth lab on your great-grandmother’s
Chippendale dining table.
Yet until now, researchers knew little
lipid dramatically increase, reflecting the
about the composition and role of these
viruses’ need for more PI4P lipid–enriched
hijacked membranes in the viral life cycle.
membrane surface to anchor their replicaNihal Altan-Bonnet and her group at Rutgers
tion machinery. If PI4P lipid production is
University have now shown that three difstopped—say, by blocking the PI4-kinase—
ferent disease-causing viruses—poliovirus,
the viruses cannot replicate, says AltanCoxsackievirus, and hepatitis C—all rely on
Bonnet.
membrane platforms enriched in a specific
The group also found that these very
lipid. The sought-after lipid is phosphatisame PI4P lipid–enriched membranes are
dylinositol 4-phosphate (PI4P). The viruses
highly enriched in cholesterol. Normally,
also carry proteins to snare one of the host’s
cholesterol regulates membrane fluidity
lipid-modifying enzymes, a type III PI4and elasticity, generating domains to sekinase, which the viruses need to generate
quester proteins so they can better interact.
the PI4P lipid for the replication platform.
Altan-Bonnet believes that PI4P lipid and
As bad as this is for the host, Altan-Bonnet
cholesterol together may generate “sticky”
says that this discovery makes PI4-kinase
membrane domains, which viruses exploit
an excellent target for panviral therapeutics.
for replication. Because viral proteins are
When the researchers blocked this PI4relatively few after they invade the host, havkinase, the poliovirus, Coxsackievirus, and
ing a “sticky” rallying point could be crucial.
hepatitis C virus all ceased replicating. Their
Moreover, the researchers discovered that
host cells survived. The Rutgers group is
viral RNA polymerases, which are vital for
extending its investigations to see how many
viruses to synthesize their own nucleic acids,
other viruses might be vulnerable to this
have specific binding sites that lock onto
countermeasure.
PI4P lipids.
Altan-Bonnet says that in the absence
In all, the hijacked PI4P lipid–cholesterol
of virus, the level of PI4P lipid is generally
domains on host membranes serve viruses as
low on organelle membranes, rising only
workshops, meet-up points, and even shieldwhen signaling and membrane-remodeling
ing against the cell’s defenses. Cutting off
proteins need to be recruited to a site. But in
their supply of stolen kinases could break the
virally infected cells, the host levels of PI4P
viral grip, say the Rutgers researchers.
The
A m er ica n
s o c i e t y
fo r
C e ll
B i o l o g y | 9
The American Society
for Cell Biology
51st Annual Meeting
Denver, Colorado
December 3–7, 2011
EMBARGOED
FOR RELEASE
10:00 am, U.S. Mountain Time
Wednesday, December 7, 2011
Contact
Nihal Altan-Bonnet, PhD
Department of Biological
Sciences
Rutgers University
Room 501B/512
225 University Ave.
Newark, NJ 07102
973-353-3483
[email protected].
edu
Author presents
Wednesday, December 7, 2011
10:15 am–10:35 am
Minisymposium: Cell-Pathogen
Interactions (Viruses and
Bacteria)
Presentation: 180
Room: 605
Viral Interior Design: Rewiring
the Host to Generate Organelle
Platforms for Replication
N. Altan-Bonnet,1 N.-Y. Hsu,2
O. Ilnytska,2 Y.-H. Chen,2
D. Boehr,3 C. Cameron3
1 Department of Biological
Sciences, Rutgers University,
Newark, NJ
2 Rutgers University, Newark, NJ
3 Pennsylvania State University,
University Park, PA
This research was supported
by grants from the National
Science Foundation and the
National Institutes of Health.