Immune responses and pathogenic events resulting from high viral replication during acute HIV infection determine the levels of HIV in late infections, and effect or control the emergence of occasional individuals who are able to control HIV without drug therapy. Observations that the initiation of antiretroviral therapy (ART) during acute infection may permit patients to subsequently control HIV without ART also indicate that critical pathogenic events are operative during acute infection. These events include impaired development of HIV-specific CD4 cells, defective antigen presentation, and hyperactivation of T cells with disruptions in T cell production and turnover. Project 3 examines the immunopathology of CD4 cell failure at the clonal level in a selected group of intensively studied subjects, through the use of class II tetramers, and an analysis of functional responses to HIV peptide matrixes as measured by intracellular cytokine production, ELISPOT, and peptide-stimulated lymphocyte proliferation. The experiments also will incorporate measurements obtained in patients participating in project 1. We will determine whether clones are deleted, rendered anergic or only partially responsive, and whether they are entering an apoptosis pathway. This project will also explore the inhibition of CD4 responses to HIV envelope by antibodies to gp120, the specificity of escape from neutralizing antibody in early infection, and whether this escape is influenced by the presence of functional HIV-specific CD4 cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI057127-02
Application #
7063463
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Project Start
Project End
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
2
Fiscal Year
2005
Total Cost
$280,928
Indirect Cost
Name
New York University
Department
Type
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Miller, Elizabeth; Spadaccia, Meredith; Sabado, Rachel et al. (2015) Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy. Vaccine 33:388-95
Gornalusse, German G; Mummidi, Srinivas; Gaitan, Alvaro A et al. (2015) Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor. Proc Natl Acad Sci U S A 112:E4762-71
Miller, Elizabeth A; Spadaccia, Meredith R; Norton, Thomas et al. (2015) Attenuated Listeria monocytogenes vectors overcome suppressive plasma factors during HIV infection to stimulate myeloid dendritic cells to promote adaptive immunity and reactivation of latent virus. AIDS Res Hum Retroviruses 31:127-36
Miller, Elizabeth; Bhardwaj, Nina (2013) Dendritic cell dysregulation during HIV-1 infection. Immunol Rev 254:170-89
Koblin, Beryl A; Mayer, Kenneth H; Noonan, Elizabeth et al. (2012) Sexual risk behaviors, circumcision status, and preexisting immunity to adenovirus type 5 among men who have sex with men participating in a randomized HIV-1 vaccine efficacy trial: step study. J Acquir Immune Defic Syndr 60:405-13
Miller, Elizabeth A; Spadaccia, Meredith R; O?Brien, Meagan P et al. (2012) Plasma factors during chronic HIV-1 infection impair IL-12 secretion by myeloid dendritic cells via a virus-independent pathway. J Acquir Immune Defic Syndr 61:535-44
Stein, Dylan; Silvera, Richard; Hagerty, Robert et al. (2012) Viewing pornography depicting unprotected anal intercourse: are there implications for HIV prevention among men who have sex with men? Arch Sex Behav 41:411-9
O'Brien, Meagan; Manches, Olivier; Sabado, Rachel Lubong et al. (2011) Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-?-producing and partially matured phenotype. J Clin Invest 121:1088-101
Sabado, Rachel Lubong; O'Brien, Meagan; Subedi, Abhignya et al. (2010) Evidence of dysregulation of dendritic cells in primary HIV infection. Blood 116:3839-52
El Hed, Aimee; Khaitan, Alka; Kozhaya, Lina et al. (2010) Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection. J Infect Dis 201:843-54

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