The Tissue Analysis Core of this U19 proposal will provide established histologic and molecular analyses of tissues obtained in each of the projects. Tissues will be processed at the time of collection with samples partitioned and stored according to standard protocols that will be developed and supplied by this Core. Drs. Schacker and Estes will develop specialized staining techniques (i.e., double or triple labels using either chromagenic or fluorescent antibodies) as needed over the duration of the grant period. They have appropriate expertise and laboratory support to accomplish these goals. The Core will provide quantitative analysis of specified features of tissues obtained by each of the projects. This will include quantitative analysis of the size of specific cell populations (identified by chromagenic or fluorescent antibody staining) in a specified anatomic location (e.g., the frequency of macrophages in the parafollicular T cell zone). Quantitative data from these analyses will be combined with other analyses to identify location and frequency of specific cell phenotypes not readily identified by immuno-histochemistry (e.g., combining the size of the total CD4+ T cell population in lymph node with flow cytometry data that measures the relative size of the naive subset of CD4+ T cells can provide an estimate of the absolute size of the naive CD4+ T cell in that tissue). The Core will provide specialized techniques for identifying the location and phenotype of cells that are either vDNA+ or vRNA+, including in situ hybridization (vRNA+ cells) and in situ PCR (vDNA+ cells). Combining either of these two in situ techniques with immunohistochemistry allows identification of the exact phenotype of cells that are infected. Whole organ analysis to identify locations of vRNA+ cells will be done in brain, lung, kidney, liver, adrenals, organs of the GU tract, and the entire gut (mouth to anus) to assist in identification of reservoirs of persistent replication. Molecular analyses of all tissues will be performed to measure the frequency of vDNA+ cells and the frequency of 2-LTR circles and integrated DNA. Collectively these data will be used to estimate 1) sites of persistent replication while on suppressive ARV and 2) size and location of reservoirs of cells harboring latent infection.

Public Health Relevance

This Core will locate and describe sites of persistent and latent infection and assist the investigators with tissue analysis. This will lead to a more complete understanding of how eradication of HIV might be accomplished.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
Delagrèverie, Héloïse M; Delaugerre, Constance; Lewin, Sharon R et al. (2016) Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents. Open Forum Infect Dis 3:ofw189
Hansen, Erik C; Ransom, Monica; Hesselberth, Jay R et al. (2016) Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells. Elife 5:
Barton, Kirston; Hiener, Bonnie; Winckelmann, Anni et al. (2016) Broad activation of latent HIV-1 in vivo. Nat Commun 7:12731
Murray, Alexandra J; Kwon, Kyungyoon J; Farber, Donna L et al. (2016) The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence. J Immunol 197:407-17
Crowell, Trevor A; Fletcher, James Lk; Sereti, Irini et al. (2016) Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation. J Int AIDS Soc 19:21163
Yong, Yean K; Shankar, Esaki M; Solomon, Ajantha et al. (2016) Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy. AIDS 30:2159-68
Siliciano, Janet D; Siliciano, Robert F (2016) Recent developments in the effort to cure HIV infection: going beyond N = 1. J Clin Invest 126:409-14
Phillips, Andrew N; Cambiano, Valentina; Revill, Paul et al. (2016) Identifying Key Drivers of the Impact of an HIV Cure Intervention in Sub-Saharan Africa. J Infect Dis 214:73-9
Sattentau, Quentin J; Stevenson, Mario (2016) Macrophages and HIV-1: An Unhealthy Constellation. Cell Host Microbe 19:304-10
Massanella, Marta; Fromentin, Rémi; Chomont, Nicolas (2016) Residual inflammation and viral reservoirs: alliance against an HIV cure. Curr Opin HIV AIDS 11:234-41

Showing the most recent 10 out of 133 publications