Research Description:
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The research in my laboratory focuses on understanding the functions of virus-host
molecular interactions that occur during infections with West Nile virus (a flavivirus)
or simian hemorrhagic fever virus (an arterivirus). Viruses utilize cell proteins
during many stages of their replication cycles, such as during attachment/entry,
translation, transcription/replication, and assembly. Such virus-host interactions
represent novel targets for the development of new antiviral agents. Since flaviviruses
replicate in mosquitoes, birds and mammals during their natural cycles, it is
expected that the cell proteins that these viruses utilize will be evolutionarily
conserved proteins. We have focused on the identification and characterization
of cell proteins that interact specifically with the 3’ terminal promoter
regions of viral genomic and anti-genomic RNAs. Two cell proteins that interact
with flavivirus RNAs have so far been identified and recent studies with knock-out
cells and a West Nile virus infectious clone indicate that the interactions of
the viral RNAs with these cell proteins facilitate virus replication. Two cell
proteins that interact specifically with the 3’ sequence of the simian hemorrhagic
fever virus genome have also recently been identified. Current studies are focused
on defining the functions of these cell protein-viral RNA interactions.
Genetic resistance to flaviviruses in mice is controlled by the alleles of
a single locus, designated Flv. This gene provides the opportunity
to study a natural mutation in a host protein that can alter the outcome of
a flavivirus infection. The Flv gene was recently identified by a positional
cloning approach as Oas1b. Current studies are focused on analysis of the mechanism
by which the products of the different alleles of this gene differentially and
specifically affect flaivivirus replication.
Recent Publications:
Maines, T. R., Young, M., Dinh, N.N.-N. and Brinton, M.A. 2005. Two cellular proteins that interact with a stem loop in the simian hemorrhagic fever virus 3 (+) NCR RNA. Virus Research, In Press.
Elghonemy, S., Davis, W.G., and Brinton, M.A. 2005. The majority of the nucleotides in the top loop of the genomic 3 terminal stem loop structure are cis-acting in a West Nile virus infectious clone. Virology, 331: 238-246.
Perelygin, A.A., Lear, T.L., Zharkikh, and Brinton, M.A. 2005. Structure of equine 2-5 oligoadenylate synthetase (Oas) gene family and FISH mapping of Oas genes to ECA8p15-p14 and BTA17q24-25. 2004. Cytogenetic and Genome Research , In Press.
Monath, T.P., Kanesa-thasan, N., Guirakhoo, F., Pugachev, K., Almond, J., Lang, J., Quentin-Millet, M.J., Barrett, A.D.T., Brinton, M.A., Cetron, M.S., Barwick, R.S., Chambers, T.J., Halstead, S.B., Roehrig, J.T., Kinney, R.M., Rico-Hesse, R., and Strauss, J.H. 2005. Recombination and flavivirus vaccines: a commentary. Vaccine, In Press.
Coutelier, J.-P and Brinton, M.A. 2005. Lactate dehydrogenase-elevating virus. In: The Mouse in Biomedical Research, Academic Press, In Press.
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