Abstract

While highly active anti-retroviral therapy (HAART) can suppress HIV-1 replication, treatment currently doesnot eradicate infection or prevent a low level of continued replication. The major objective of this project isdirected to defining the anatomic and cellular compartments in which HIV-1 is produced and persists beforeand during HAART, and from which infection re-emerges on discontinuation of HAART.
The Specific Aim ofthe project is to identify, characterize and quantify cellular sources of virus production and persistence in gutassociatedlymphatic tissues (GALT) and peripheral lymphatic tissues (LTs), using state-of-the-art in situTechnologies of in situ hybridization, in situ PCR, immunohistochemistry and quantitative image analysis,with the long-term goal of capitalizing on the new insights into HIV-1 reservoirs generated by this analysis todesign even more effective treatments.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI074340-01A2
Application #
7577040
Study Section
Special Emphasis Panel (ZAI1-CCH-A (M1))
Project Start
2008-09-30
Project End
2013-08-31
Budget Start
2008-07-01
Budget End
2009-08-31
Support Year
1
Fiscal Year
2008
Total Cost
$322,320
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Kityo, Cissy; Makamdop, Krystelle Nganou; Rothenberger, Meghan et al. (2018) Lymphoid tissue fibrosis is associated with impaired vaccine responses. J Clin Invest 128:2763-2773
Estes, Jacob D; Kityo, Cissy; Ssali, Francis et al. (2017) Defining total-body AIDS-virus burden with implications for curative strategies. Nat Med 23:1271-1276
Cory, Theodore J; He, Hui; Winchester, Lee C et al. (2016) Alterations in P-Glycoprotein Expression and Function Between Macrophage Subsets. Pharm Res 33:2713-21
Lorenzo-Redondo, Ramon; Fryer, Helen R; Bedford, Trevor et al. (2016) Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 530:51-56
Sanchez, Joyce L; Hunt, Peter W; Reilly, Cavan S et al. (2015) Lymphoid fibrosis occurs in long-term nonprogressors and persists with antiretroviral therapy but may be reversible with curative interventions. J Infect Dis 211:1068-75
Cory, Theodore J; Winchester, Lee C; Robbins, Brian L et al. (2015) A rapid spin through oil results in higher cell-associated concentrations of antiretrovirals compared with conventional cell washing. Bioanalysis 7:1447-55
Winchester, Lee C; Podany, Anthony T; Baldwin, Joshua S et al. (2015) Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS. J Pharm Biomed Anal 104:55-61
Mitchell, Caroline; Roemer, Emily; Nkwopara, Evangelyn et al. (2014) Correlation between plasma, intracellular, and cervical tissue levels of raltegravir at steady-state dosing in healthy women. Antimicrob Agents Chemother 58:3360-5
Fletcher, Courtney V; Staskus, Kathryn; Wietgrefe, Stephen W et al. (2014) Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 111:2307-12
Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J et al. (2014) Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity. Cancer Med 3:81-90

Showing the most recent 10 out of 30 publications