Host immune response to viral infection, the basis of persistent viral infection in reservoir hosts, host-pathogen interactions, and the development of novel therapeutic agents and vaccines
The arenaviruses and hantaviruses are rodent-borne pathogens that cause significant morbidity and mortality in humans. Arenaviruses cause illnesses ranging from aseptic meningitis following infection with lymphocytic choriomeningitis virus (LCMV) to hemorrhagic fever syndromes following infection with Lassa, Junin, Machupo, and Guanarito viruses, whereas hantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a disease that carries a 30 – 50% mortality rate in the Americas. Viruses in both genera have RNA genomes that encode four open reading frames in either negative sense (hantavirus) or ambisense (arenavirus) fashion. Currently there are no licensed vaccines available for the prevention of arenavirus or hantavirus disease. Dr. Botten’s research interests pertaining to these viruses include understanding how the host immune response contributes to pathogenesis and/or protective immunity, identifying novel host-pathogen interactions, understanding how these viruses regulate their replicative activity to establish persistent infection in reservoir rodents, and developing novel therapeutic agents and vaccines.
The world’s first outdoor biosafety level-4 laboratory for studies of deer mice infected with Sin Nombre hantavirus
Botten, J. Whitton, J. L., Barrowman, P., Sidney, J., Whitmire, J. K., Alexander, J., Kotturi, M., Sette, A., and Buchmeier, M. (2010) A universal human vaccine for pathogenic Old World arenaviruses. Journal of Virology; 84, 9947-9956.
Kotturi, M. F., Botten, J., Maybeno, M., Sidney, J., Glenn, J., Bui, H. H., Oseroff, C., Crotty, S., Peters, B., Grey, H., Buchmeier, M. J., and Sette A. (2010) Polyfunctional CD4+ T cell responses to a set of pathogenic arenaviruses provide broad population coverage. Immunome Research: May 17, 6:4.
Botten, J., Sidney, J., Mothe, B., Peters, B., Sette, A., and Kotturi, M. (2010) Coverage of related pathogenic species by conserved versus multivalent epitope design. Arenaviruses as a model system. Microbiology and Molecular Biology Reviews; 74, 157-70.
Alexander, J., Bilsel, P., del Guercio, M., Stewart, S., Marinkovic-Petrovic, A., Southwood, S., Crimi, C., Vang, L., Walker, L., Ishioka, G., Chitnis, V., Sette, A., Assarsson, E., Hannaman, D., Botten, J., Newman, M. (2010) Universal Influenza DNA Vaccine Encoding Conserved CD4+ T Cell Epitopes Protects Against Lethal Viral Challenge in HLA-DR Transgenic Mice. Vaccine; 28, 664-672.
Kotturi, M. F., Botten, J., Sidney, J., Bui, H. H., Giancola, L., Maybeno, M., Babin, J., Oseroff, C., Pasquetto,. V., Greenbaum, J. A., Peters, B., Ting, J., Do, D., Vang, L., Alexander, J., Grey, H., Buchmeier, M. J., and Sette A. (2009) A multivalent and cross-protective vaccine strategy against arenaviruses associated with human disease. PLoS Pathogens, 5:e1000695.
Botten, J., Whitton, J. L., Barrowman, P., Sidney, J., Whitmire, J. K., Alexander, J., Ting, J., Bui, H., Sette, A., and Buchmeier, M. J. (2007) HLA-A2-restricted protection against lethal lymphocytic choriomeningitis. Journal of Virology; 81, 2307-2317.
* indicates equal contribution
Ruth L. Kirschstein National Research Service Award for Individual Postdoctoral Fellows (2003-2005)
Joel M. Dalrymple Award, American Society of Virology (2002)
Department of Medicine
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