Abstract

Significant advances were made in discovering the mechanisms of retrovirus-induced immunosuppression in the Friend virus model. We discovered a new form of retrovirus-induced immunosuppression that was mediated by regulatory T cells. Regulatory T cells were found to be induced by chronic infections and rendered the mice incapable of rejecting certain tumor cell transplants. These findings form a conceptual link between virus-induced immunosuppression and autoimmune diseases. Aslo, these results may have relevance to some types of immunosuppression induced when humans are infected with human immunodeficiency virus. We also made significant advances in elucidating how CD4+ T cells control chronic retroviral infection. Two mechanisms were discovered, direct cytolysis of infected cells, and suppression of virus production by infected cells by secretion of gamma interferon. We also used mice with targeted genetic inactivations to probe the roles of several cytokines in both natural recovery from acute infection and in vaccine induced protection from infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000753-06
Application #
6531644
Study Section
(LPVD)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
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
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
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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