Abstract

The murine model MAIDS is used to ask fundamental questions about the mechanisms of retroviral pathogenesis. MAIDS induces a immunosuppression of both B and T lymphocyte responses, polyclonal B cell activation and hypergammaglobulinemia, lymphadenopathy, increased susceptibility to opportunistic infections and an increased incidence of non-Hodgkin's B cell lymphomas. The overall goals of this proposal are to examine: (1) CD40L mediated signaling o B cells leading to their activation, hypergammaglobulinemia and ultimately B cell tumors; (2) the specificity of cytotoxic T cells (CTL) responses of MAIDS-resistant mouse strains or to an immunodominant gag epitope; and (3) the potential contribution of open reading frame (ORF2) directed expression of this gag epitope. The experimental approach utilizes CD40 or CD40L knock out mice to examine the role of these molecules in the genesis of disease, and mutational analysis of ORF2 and CTL epitopes to examine immune resistance and susceptibility.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA050157-07
Application #
2717450
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Cremer, Kenneth J
Project Start
1990-03-01
Project End
2003-04-30
Budget Start
1998-07-08
Budget End
1999-04-30
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Dartmouth College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755

  Publications

Rastad, Jessica L; Green, William R (2016) Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-?. Virology 499:9-22
O'Connor, Megan A; Vella, Jennifer L; Green, William R (2016) Reciprocal relationship of T regulatory cells and monocytic myeloid-derived suppressor cells in LP-BM5 murine retrovirus-induced immunodeficiency. J Gen Virol 97:509-22
Green, Kathy A; Wang, Li; Noelle, Randolph J et al. (2015) Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell, but Not T-Cell, Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus. J Virol 89:9693-8
O'Connor, Megan A; Fu, Whitney W; Green, Kathy A et al. (2015) Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses. Virology 485:263-73
O'Connor, Megan A; Green, William R (2014) Use of IRF-3 and/or IRF-7 knockout mice to study viral pathogenesis: lessons from a murine retrovirus-induced AIDS model. J Virol 88:2349-53
O'Connor, Megan A; Green, William R (2013) The role of indoleamine 2,3-dioxygenase in LP-BPM5 murine retroviral disease progression. Virol J 10:154
Green, Kathy A; Cook, W James; Green, William R (2013) Myeloid-derived suppressor cells in murine retrovirus-induced AIDS inhibit T- and B-cell responses in vitro that are used to define the immunodeficiency. J Virol 87:2058-71
Rutkowski, Melanie R; Stevens, Cynthia A; Green, William R (2011) Impaired memory CD8 T cell responses against an immunodominant retroviral cryptic epitope. Virology 412:256-68
Li, Wen; Green, William R (2011) Immunotherapy of murine retrovirus-induced acquired immunodeficiency by CD4 T regulatory cell depletion and PD-1 blockade. J Virol 85:13342-53
Li, Wen; Carlson, Timothy L; Green, William R (2011) Stimulation-dependent induction of CD154 on a subset of CD4+ FoxP3+ T-regulatory cells. Int Immunopharmacol 11:1205-10

Showing the most recent 10 out of 31 publications