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Scientific Report 2006
Molecular Biology
Nanomanufacturing on an Icosahedral Scaffold and Neutralization of Avian H5N1 Influenza Viruses
T. Lin, J.E. Johnson, A. Censullo, A. Chatterji
Molecular Electronics on an Icosahedral Scaffold
Molecular manufacturing, the essence
of nanotechnology, involves the manipulation of molecules as the self-assembling
components at the nanometer scale to build devices in mesoscale. Although small
molecules with novel electronic properties can be synthesized, making functional
connectivity among the different components in designed patterns is generally difficult.
In contrast, biological macromolecules are more amenable for self-assembly because
of their versatility, programmability through genetic engineering, and propensity
to form arrays and can be used either directly as devices or as scaffolds for patterning
small molecules.
We have shown that cowpea mosaic
virus (CPMV), an icosahedral plant virus, can be used as the template for nanochemistry
by introducing unique cysteine residues and exploiting the native lysine residues.
In collaborative studies with B.R. Ratna, Naval Research Laboratory, Washington,
D.C., the virus capsid was exploited as a nano circuit board, and the reactive groups
were used as anchoring points for the assembly of the electronic molecules oligophenylene-vinylene
and 1,4-C6H4[trans-(4-AcSC6H4ºCPt(Pbu3)2ºC]2.
The establishment of the molecular network was shown by measuring electronic conductance
with scanning tunnel microscopy.
Neutralization of Avian H5N1 Influenza Viruses
Influenza is one of the most important
viral diseases in humans. It has caused morbidity and mortality in millions of people
in frequent epidemics and pandemics throughout the centuries. Human influenza virus
is typically associated with 3 H subtypes: H1, H2, and H3. In recent years, an avian
H5 (H5N1) influenza virus crossed the species barrier to infect humans with high
virulence. To date, the avian virus has not been efficient in transmission from
human to human, and the disease has not spread in the human population. However,
the continuous circulation and spreading of H5N1 viruses in avian species across
the globe leads to more human infections and increases the likelihood that the virus
will acquire the necessary characteristics for efficient human-to-human transmission
through genetic mutation or reassortment with a prevailing human influenza A virus.
The possible emergence of an H5N1
virus highly contagious to humans is a serious pandemic threat. Therefore, producing
effective vaccines to counter the threat posed by the H5N1 viruses is important.
CPMV is an effective scaffold for the development of subunit vaccines. We are developing
a novel combinatorial strategy in which the CPMV system is used to identify vaccine
candidates.
In another study in collaboration
with scientists in Hong Kong and Southern China, the epicenter of the influenza
outbreaks, we have produced more than 100 monoclonal antibodies against the avian
influenza viruses and have shown that many of these antibodies are neutralizing.
These neutralizing antibodies are used in the analysis of escape mutants in conjunction
with the vaccine development. Structural studies of antibody interactions with the
H5N1 viruses are also being carried out to shed light on the mechanism of neutralization
of the viruses.
Publications
Medintz, I.L., Sapsford, K.E.,
Konnert, J.H., Chatterji, A., Lin, T., Johnson, J.E., Mattoussi, H.
Decoration of discretely immobilized cowpea mosaic virus with luminescent quantum
dots. Langmuir 21:5501, 2005.
Prasad, T., Turner, M., Falkner,
J., Mittleman, D., Johnson, J.E., Lin, T., Colvin, V. Nanostructured
virus crystals for x-ray optics. IEEE Trans. Nanotechnol., in press.
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