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When the human body becomes infected with new
influenza viruses, the immune system rapidly activates
an inborn protective mechanism to inhibit the intruding
pathogen. A protein known as Mx plays an important role
in this process, keeping the spread of viruses in check.
Exactly how Mx accomplishes this task was previously
unknown. Now virologists from the Institute of Medical
Microbiology at the Freiburg University Medical Center
and structural biologists from the Max Delbrück
Center for Molecular Medicine (MDC) in Berlin-Buch,
Germany, have unraveled the structure of the Mx protein and
are able to explain how it develops its anti-viral effect
(Nature, doi: 10.1038/nature08972)*.
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New influenza viruses jump from animals to humans
with alarming frequency, as evidenced by the H5N1
bird flu virus or, more recently, with the swine flu virus.
Although humans usually do not have any preexisting
immunity to such pathogens, they are not completely
unprotected against the invaders. The human body can
rapidly mobilize a defense strategy which prevents the
influenza viruses from proliferating unchecked in the body.
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An essential element of this protection is a protein,
known as Mx (short for myxovirus resistance), produced
by the body which recognizes many viruses and prevents
them from replicating inside infected cells. Under normal
conditions this protective protein is not present in the cell
at all, but after infection it can be produced in large quantities.
The order to produce this protein Mx is made by the
signaling protein interferon, which is excreted by infected
cells and alarms the organism of the virus infection.
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Mx is a molecular machine which does not develop
its full power until the individual molecules have joined
to form a ring-structured macromolecular network. A
central element of the formation of these ring structures
is the special part of Mx known as the stalk.
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Scientists have attempted to describe the structure
of this stalk for years. The virologists Otto Haller,
Alexander von der Malsburg, and Georg Kochs in Freiburg
and the structural biologists Oliver Daumke, Song Gao,
Susann Paeschke, and Joachim Behlke from MDC in
Berlin-Buch have now unraveled the secret of the stalk structure
of Mx at the atomic level. This structure explains the
composition of Mx and allows scientists to conduct tests to
make predictions concerning the mode of action of the
antiviral molecule.
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In combination with findings from earlier biochemical
studies, the results of this study make it clear that the
stalk structure of Mx functions as a kind of clamp which
restrains and deactivates important components of the
influenza virus in the infected cell. The fact that new forms
of flu can lead to epidemics or even pandemics in spite
of this defense mechanism is due to the power and
aggressiveness of these pathogens.
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The researchers are confident that their new findings
about the protective Mx protein will form the basis for the
development of new antiviral drugs for combating
dangerous influenza viruses. Moreover, they are also
certain that this new knowledge about the function of Mx
will increase their understanding of other members of this
family of proteins.
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A computer model of the protein may be downloaded at:
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http://www.mdc-berlin.de/de/index.html
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