The purpose of this project is to investigate the genetics and immunology of resistance to retroviral infection. The model I use is mice infected with muringe leukemia viruses. Both innate resistance and induced resistance are studied. Genetically defined mouse strains such as congenic, congenic recombinant, transgenic, and knockout strains are used to identify resistance genes, and to relate genetic resistance to specific immunological mechanisms. In addition, we also use these mice to investigate mechanisms of vaccine-induced protection against both acute disease and persistent retroviral infections. The work basically involves determining which types of cells are involved in protective responses versus the types of cells involved in non-protective or even harmful responses, and determining what these various cells are doing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000753-05
Application #
6431665
Study Section
(LPVD)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Velmourougane, Geetha; Harbut, Michael B; Dalal, Seema et al. (2011) Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase. J Med Chem 54:1655-66
Pike, Rebecca; Filby, Andrew; Ploquin, Mickael J-Y et al. (2009) Race between retroviral spread and CD4+ T-cell response determines the outcome of acute friend virus infection. J Virol 83:11211-22
Ammann, Christoph G; Messer, Ronald J; Peterson, Karin E et al. (2009) Lactate dehydrogenase-elevating virus induces systemic lymphocyte activation via TLR7-dependent IFNalpha responses by plasmacytoid dendritic cells. PLoS One 4:e6105
Robertson, Shelly J; Messer, Ronald J; Carmody, Aaron B et al. (2008) CD137 costimulation of CD8+ T cells confers resistance to suppression by virus-induced regulatory T cells. J Immunol 180:5267-74
Greene, Justin M; Burwitz, Benjamin J; Blasky, Alex J et al. (2008) Allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques. PLoS One 3:e2384
Santiago, Mario L; Montano, Mauricio; Benitez, Robert et al. (2008) Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science 321:1343-6
Marques, Rute; Antunes, Ines; Eksmond, Urszula et al. (2008) B lymphocyte activation by coinfection prevents immune control of friend virus infection. J Immunol 181:3432-40
Robertson, Shelly J; Ammann, Christoph G; Messer, Ronald J et al. (2008) Suppression of acute anti-friend virus CD8+ T-cell responses by coinfection with lactate dehydrogenase-elevating virus. J Virol 82:408-18
Hasenkrug, Kim J; Dittmer, Ulf (2007) Immune control and prevention of chronic Friend retrovirus infection. Front Biosci 12:1544-51
Hasenkrug, Kim J (2007) The leptin connection: regulatory T cells and autoimmunity. Immunity 26:143-5

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