- Paredes, A. M., Alwell-Warda, K., Weaver, S. C., Chiu, W. Watowich, S. J. (2001) Venezuelan equine encephalomyelitis virus structure and its divergence from old world alphaviruses. J. Virology, 75:9532-9537.
- Paredes, A. M., Alwell-Warda, K., Weaver, S. C., Chiu, W. Watowich, S. J. (2003) Structure of isolated nucleocapsids from Venezuelan equine encephalitis virus and implications for assembly and disassembly of enveloped viruses. J. Virology, 77: 659-664.
- Paredes, A. M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., and Brown, D. T. (2004) Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2): 373-86.
- Paredes, A. M., Weaver, S., Watowich, S., Chiu, W. (2005) Structural biology of old world and new world alphaviruses. Arch Virol Suppl 19: 179-85.
- Schmid, M. F., Paredes, A. M., Khant, H. A., Soyer, F., Aldrich, H. C., Chiu, W., Shively, J. M., (2006) Structure of Halothiobacillus neapolitanus carboxysomes by electron tomography. J. Molec. Biol., .364: 526-35.
- Hernandez, R., Paredes, A. M., West, M., Brown, D. T. (2007) Electron cryomicroscopic reconstruction of Sindbis virus conformational changes induced by a neutralizing anti-E1 antibody. In preparation.
Angel Paredes, PhD
Pathology & Laboratory Medicine
(713) 500 - 7281
The central goal of my research is to use high resolution electron cryomicroscopy to explore the biology of alphavirus replication including assembly and the host-virus interactions that are necessary for infection. Because the spike proteins are embedded in a host-derived lipid bilayer, alphaviruses also provide us with an excellent model for studying native membrane proteins and their interactions with a lipid bilayer. I am presently working to improve the resolution of the structural information from alphaviruses by using a powerful 300 kV electron cryomicroscope capable of near atomic resolution (~3.5 Å) along with a robust image processing software that takes advantage of the highly symmetrical and well preserved nature of this virus to achieve high resolution.
Understanding how alphaviruses infect their hosts is necessary for future therapeutic development. Alphaviruses are an important group of pathogens, because they are arboviruses that transmit disease through the bite of infected mosquitoes. The disease that they cause is characterized by a range of symptoms from mild flu-like symptoms to full blown encephalitis with sometimes permanent neurological sequelae and even death. The mosquito vectors responsible for transmission are predominantly found in the tropic and sub-tropic regions of the world. In the United States, the southern states are particularly vulnerable to regional epidemics. With global warming becoming an increasing concern in the United States, the threat can only spread northward. The application of electron microscopy and other techniques will improve our understanding of alphavirus structure and host-virus interactions, and may lead to the identification of specific targets for anti-viral agents or vaccines.
Graduate students or undergraduate trainees working in my laboratory will gain experience in virus propagation and isolation, principles and operation of high resolution electron microscopes, and the use of computer algorithms to construct three-dimensional structures of virus particles.