ASCB 2013 PressBook - page 10

T H E A M E R I C A N S O C I E T Y F O R C E L L B I O L O G Y
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News from
The American Society
for Cell Biology
53rd Annual Meeting
New Orleans, LA
December 14–18, 2013
Dialing down the flu
EMBARGOED
FOR RELEASE
10:00 am, U.S. Central Time
Sunday, December 15, 2013
Contact
Amy L. Adamson
Room 201 Eberhart Building
Biology Department
University of North Carolina
at Greensboro
Greensboro, NC 27412
(336) 256-0312
Hinissan Pascaline Kohio
Southern Illinois University
School of Medicine
825 N. Rutledge
PO Box 19626
Springfield,IL 62794
Authors Present
Sunday, December 15, 2013
1:30 PM–3:00 PM
Host-Pathogens/Host-
Commensal Interactions II
Presentation 2266
Poster B1250
Session P105
Abstract 312
Exhibit Halls B–D
Glycolytic Control of Vacuolar-
Type ATPase Activity: A
Mechanism to Regulate
Influenza Viral Infection
H. P. Kohio, A. L. Adamson
Biology, University of North
Carolina Greensboro,
Greensboro, North Carolina
Turning down glucose metabolism
in cells slows influenza infection,
suggesting a new strategy for
flu therapy
F
ever, ache, and the other miseries of
influenza viral infection afflict 5−20
percent of the U.S. population each
year. The “flu” is usually not life-threatening
to the majority of its victims, but as the Span-
ish flu pandemic of 1918 showed, flu viruses
can evolve into lethal agents and spread
worldwide. The ability of flu viruses to change
continually through mutation and genetic
swaps is the reason that the Centers for
Disease Control and Prevention(CDC) re-
formulates the flu vaccine each year, hoping
to block the types and subtypes of influenza
viruses that they believe are most likely to be
in circulation.
Yet to infect cells, the influenza virus is
dependent upon the actions of the cell’s own
proteins, and so another strategy for slowing
viral infection would be to target essential
viral needs, for example, their dependence
on cellular glucose. Which is what Amy
Adamson and Hinissan Pascaline Kohio of
the University of North Carolina, Greens-
boro, have done, showing that they could
control influenza A infection in laboratory
cultures of mammalian cells by altering
glucose metabolism.
When the influenza virus initially infects
a cell, and the virus is confined in an endo-
cytic vesicle, the viral proteins HA and M2
use the acidic environment found inside the
vesicle to fuse the viral lipid envelope with
that of the vesicle, and then release the viral
genome into the cytosol. The acidic pH
that mediates these impor-
tant viral events is estab-
lished and maintained by
the cell’s vacuolar-type H+
ATPase (V-ATPase) proton
pump. The researchers
found that this dependence
could be used to manipu-
late infection success.
First, Adamson and
Kohio boosted glucose
concentrations in the cell
cultures, and influenza in-
fection rate concomitantly
increased. But treating the
viral cells with a chemical
that inhibits glucose
metabolism significantly
High glucose levels induce assembly of the V
1
V0-ATPase within cells—
this correlates with higher viral infection.
decreased viral replication in the lab cul-
tures. Further, the researchers demonstrat-
ed that the infection could be restored to
high levels simply by adding ATP, the major
source of energy for cellular reactions,
bypassing the need for glucose.
Looking closer, they discovered that
higher levels of glucose promoted the
assembly of the V-ATPase proton pump
that drives the release of the influenza A
genome into the cytoplasm, the internal
watery environment of the cell. When
Adamson and Kohio added the glucose
inhibitor to the cell cultures, assembly of
the molecular pump was suppressed. Viral
infection, they concluded, was closely tied
to the assembly of the V-ATPase pump, and
this dependence could be used to manipu-
late infection success.
Specifically, they could suppress vi-
ral infection of cells by dismantling the
V-ATPase through the lowering of glucose
levels. In addition, they could inhibit infec-
tion by treating cells with chemical in-
hibitors of glycolysis, the initial pathway of
glucose catabolism. Conversely, influenza
viral infection of cells could be increased by
giving cells more glucose than normal, the
researchers report in the journal
Virology,
.
The ease with which the researchers
could dial viral infection down by control-
ling glucose levels and thus V-ATPase activ-
ity suggested a new strategy for throttling
influenza viral infection. “Taken together,
we propose that altering glucose metabo-
lismmay be a potential new approach
to inhibit influenza viral infection,” say
Adamson and Kohio.
I...,II,1,2,3,4,5,6,7,8,9 11,12,13
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