application's abstract): This application requests funds to allow the principal investigator, Dr. Peter Anton, to pursue clinical research on the quantification of mucosal viral loads and the characterization of mononuclear cells present in focal infections of HIV-1 in the intestinal mucosa. This work is based on newly developed methods in Dr. Anton's group to reproducibly isolate mucosal lympoid tissue. There are three specific aims.
In Aim 1, Dr. Anton will continue with the optimization of the technique for isolation and characterization of mucosal lymphoid tissue to test the hypothesis that HIV infection is associated with mucosal inflammation. This part of the application will focus on the isolation of mononucelar cells and on quantitative methods to measure tissue RNA/DNA for HIV-1.
In Aim 2, a study will be carried out to examine the correlation between CCR5 co-receptor expression and enhanced susceptibility to infection with HIV-1. Additionally, the relationship between HIV infection and D- chemokine expression (as a marker of inflammation) will be sought to test this hypothesis.
In Aim 3, a clinical study will be executed to test the hypothesis that inflammation is a clinically significant feature of HIV persistence. This will be done by looking for decreased mucosal viral burden and evidence of immune reconstitution after therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
1K24AI001610-01A1
Application #
6045313
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Sager, Polly R
Project Start
2000-04-01
Project End
2005-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
1
Fiscal Year
2000
Total Cost
$116,238
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Anton, Peter A; Ibarrondo, F Javier; Boscardin, W John et al. (2008) Differential immunogenicity of vaccinia and HIV-1 components of a human recombinant vaccine in mucosal and blood compartments. Vaccine 26:4617-23
Poles, Michael A; Boscardin, W John; Elliott, Julie et al. (2006) Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals. J Acquir Immune Defic Syndr 43:65-8
Fletcher, Patricia S; Elliott, Julie; Grivel, Jean-Charles et al. (2006) Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides. AIDS 20:1237-45
Shacklett, Barbara L; Yang, Otto; Hausner, Mary Ann et al. (2003) Optimization of methods to assess human mucosal T-cell responses to HIV infection. J Immunol Methods 279:17-31
Anton, Peter A; Mitsuyasu, Ronald T; Deeks, Steven G et al. (2003) Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects. AIDS 17:53-63
Anton, P A; Poles, M A; Elliott, J et al. (2001) Sensitive and reproducible quantitation of mucosal HIV-1 RNA and DNA viral burden in patients with detectable and undetectable plasma viral HIV-1 RNA using endoscopic biopsies. J Virol Methods 95:65-79
Poles, M A; Fuerst, M; McGowan, I et al. (2001) HIV-related diarrhea is multifactorial and fat malabsorption is commonly present, independent of HAART. Am J Gastroenterol 96:1831-7
Poles, M A; Elliott, J; Taing, P et al. (2001) A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection. J Virol 75:8390-9
Poles, M A; Elliott, J; Vingerhoets, J et al. (2001) Despite high concordance, distinct mutational and phenotypic drug resistance profiles in human immunodeficiency virus type 1 RNA are observed in gastrointestinal mucosal biopsy specimens and peripheral blood mononuclear cells compared with plasma. J Infect Dis 183:143-8
Keire, D A; Anton, P; Faull, K F et al. (2001) Diethyl phthalate, a chemotactic factor secreted by Helicobacter pylori. J Biol Chem 276:48847-53