UTMB Department of Pathology

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My research has focused on viral pathogenesis and vaccine/diagnostics/antivirals development. I am currently working on the following NIH-funded projects:

1. VEE pathogenesis and vaccine development (PI-Paessler)
Venezuelan equine encephalitis virus (VEEV) produces a “flu-like” human illness and encephalitic signs and symptoms, with mortality rates approaching 1%. The goals of this project are to 1) develop safe and effective VEEV vaccines using chimeric SINV/VEEV viruses that are efficiently produced at large scale, and 2) study VEEV pathogenesis using reciprocal SINV/VEEV chimeras to assess the roles of structural vs. nonstructural proteins in tissue tropism and pathogenicity.

2. Chimeric Alphaviruses for Serological VEEV Diagnostics (PI-Paessler).
Rapid and accurate diagnosis of VEE outbreak is essential to instituting appropriate control measures to limit the scope of human and equine disease. We are creating chimeric Sindbis/VEE viruses for diagnostic assays and production of immune sera to overcome the shortage of diagnostic capacity. These chimeric viruses would 1) improve safety in diagnostic laboratories by reducing the risk of laboratory-acquired infections and laboratory-initiated outbreaks, as reported for VEEV from Venezuela; 2) eliminate the need for large-scale VEEV production; 3) make VEEV serological diagnostic reagents available to local public health and private diagnostic laboratories to be used safely in a BSL-2 containment; 4) enable laboratories to safely produce high quality, VEEV-specific immune sera under BSL-2 containment using a single inoculum; and 5) improve the ability to ship diagnostic tools within and outside of the U.S.

3. Development of antivirals against VEEV (PI-Paessler).
The development of traditional antiviral drugs requires an extensive screening process and usually only applies to a single specific agent. Recently developed chemically synthesized phosphorodiamidate morpholino oligos (PMO) have many advantages over traditional antisense oligomers and function by steric blockage. In addition, PMOs are well tolerated by both humans and animals. We have shown (Dr. R. Rijnbrand was PI prior to leaving UTMB) strong inhibition of both Sindbis virus, VEEV-TC83, and VEEV ZPC738 in tissue culture. We aim to 1) confirm the inhibitory effects of VEEV-specific PMOs against a variety of VEEV strains in tissue culture and 2) determine the in vivo efficacy and therapeutic window of the PMOs in a VEEV mouse model.

4. Vaccine development against Rift Valley fever virus. (PI-Frolov).
Rift Valley fever virus (RVFV) is a representative member of the Bunyaviridae family. The RVFV is continuously circulating in livestock-raising regions of Africa. RVFV can be transmitted by many different species of mosquitoes. The main goal of our research plan is to create a vaccine that will efficiently protect livestock and humans against the disease caused by RVFV. The vaccine testing is performed by my group in our new BSL-4 laboratory (Robert Shope Laboratory) in a murine model.

5. Neuroinflammatory response-mediated VEEV clearance from the brain (in development, PI-Paessler).
Together with Drs. Mark Estes, Ilya Frolov and Scott C. Weaver, we are working on a model to study VEEV clearance from the brain. Of special interest is the development of benign and highly efficient anti-VEEV neuroinflammatory response in the model and its potential use to improve our current understanding of VEEV-caused encephalitis (submitted to J Vir). The specific characteristics of the neuroinflammation caused by VEEV need further investigation, and their understanding will lead to development of new means of therapeutic treatment of VEEV-dependent encephalitis.

1. Paessler S, Aguilar P, Anishchenko M, Wang HQ, Aronson J, Campbell G, Cararra AS, Weaver SC. The Hamster as an Animal Model for Eastern Equine Encephalitis--and Its Use in Studies of Virus Entrance into the Brain. J Infect Dis 189 (11): 2072-6, 2004
2. Weaver SC, Anishchenko M, Bowen R, Brault AC, Estrada-Franco JG, Fernandez Z, Greene I, Ortiz D, Paessler S, Powers AM. Genetic determinants of Venezuelan equine encephalitis emergence. Arch Virol Suppl (18): 43-64, 2004
3. Anishchenko M, Paessler S, Greene IP, Aguilar PV, Carrara AS, Weaver SC. Generation and characterization of closely related epizootic and enzootic infectious cDNA clones for studying interferon sensitivity and emergence mechanisms of Venezuelan equine encephalitis virus. J Virol 78 (1): 1-8, 2004
4. Passler S, Pfeffer M. Detection of antibodies to alphaviruses and discrimination between antibodies to eastern and western equine encephalitis viruses in rabbit sera using a recombinant antigen and virus-specific monoclonal antibodies. J Vet Med B Infect Dis Vet Public Health 50 (6): 265-9, 2003.
5. Paessler S, Fayzulin RZ, Anishchenko M, Greene IP, Weaver SC, Frolov I. Recombinant sindbis/venezuelan equine encephalitis virus is highly attenuated and immunogenic. J Virol 77 (17): 9278-86, 2003

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