This application has three specific aims the first of which describes a systematic approach for testing the correlation between UVD (unintegrated viral DNA) and clinical status. Frozen peripheral blood monocytic cells (PBMC) (1,500 samples) representing more than 700 well-characterized patients will be tested for UVD levels. These data will be correlated with clinical and laboratory data available for this well-characterized patient population. Rigorous statistical analysis of the data will establish the validity of UVD as a marker for disease progression in AIDS. Analysis of UVD could also provide fresh insight into the mode of antiviral action in vivo. Therapeutic agents designed to reduce HIV replication and infection should also reduce the level of UVD. Because UVD is transient in the newly-infected cell, data on drug action could be obtained over a short testing period as compared to the longer intervals required to observe changes in surrogate markers of infection. The second goal of the investigator encompasses a plan to assess drug efficacy based on changes in UVD. This will be done by temporal analyses of UVD-positive patients receiving drug for the first time and on patients who are discontinuing drug therapy. In addition to its role in acute infection of cells, unintegrated DNA is also a feature in latent macrophage infection, the subject of the last specific aim. The structural features of UVD in latently-infected monocytic cells will be examined by molecular cloning, DNA sequencing and transfection studies. In order to investigate the role of these UVD species in HIV infection, the structure of viral DNA in central nervous system tissue will be examined. In this tissue, the principal infected cell type is the macrophage and the presence of UVD has already been documented.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024591-06
Application #
2062646
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1988-09-30
Project End
1996-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Pathology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Streblow, D N; Kitabwalla, M; Pauza, C D (1998) Gag protein from human immunodeficiency virus type 1 assembles in the absence of cyclophilin A. Virology 252:228-34
Streblow, D N; Kitabwalla, M; Malkovsky, M et al. (1998) Cyclophilin a modulates processing of human immunodeficiency virus type 1 p55Gag: mechanism for antiviral effects of cyclosporin A. Virology 245:197-202
Pauza, C D; Hinds 2nd, P W; Yin, C et al. (1997) The lymphocytosis-promoting agent pertussis toxin affects virus burden and lymphocyte distribution in the SIV-infected rhesus macaque. AIDS Res Hum Retroviruses 13:87-95
Coe, C L; Reyes, T M; Pauza, C D et al. (1997) Quinolinic acid and lymphocyte subsets in the intrathecal compartment as biomarkers of SIV infection and simian AIDS. AIDS Res Hum Retroviruses 13:891-7
Trivedi, P; Horejsh, D; Hinds, S B et al. (1996) Intrarectal transmission of simian immunodeficiency virus in rhesus macaques: selective amplification and host responses to transient or persistent viremia. J Virol 70:6876-83
Scharko, A M; Perlman, S B; Hinds PW2nd et al. (1996) Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques. Proc Natl Acad Sci U S A 93:6425-30
Hinds 2nd, P W; Yin, C; Salvato, M S et al. (1996) Pertussis toxin induces lymphocytosis in rhesus macaques. J Med Primatol 25:375-81
Wallace, M; Gan, Y H; Pauza, C D et al. (1994) Antiviral activity of primate gamma delta T lymphocytes isolated by magnetic cell sorting. J Med Primatol 23:131-5
Trivedi, P; Meyer, K K; Streblow, D N et al. (1994) Selective amplification of simian immunodeficiency virus genotypes after intrarectal inoculation of rhesus monkeys. J Virol 68:7649-53
Pauza, C D; Trivedi, P; McKechnie, T S et al. (1994) 2-LTR circular viral DNA as a marker for human immunodeficiency virus type 1 infection in vivo. Virology 205:470-8

Showing the most recent 10 out of 22 publications