Abstract

The major goal of this project is to determine the role of existing viruses in the etiology of AIDS. The AIDS virus, HIV, multiplies in T4 lymphocytes, kills the cells in the process, depletes the body of T4 cells and, causes an immune deficiency. HIV can also replicate in some non-T cells. For example, in most B cell lines latently infected by Epstein- Barr virus (EBV), HIV can replicate, sometimes even in a less lytic (cell killing) fashion than in T4 cells, but HIV cannot replicate in B cells without EBV. This project will study in detail the interactions between the two viruses, HIV and EBV, when both infect the same B lymphocyte. This might mimic what happens in the body and could, possibly, lead to high and prolonged production of the AIDS virus, which could eventually lead to AIDS. We are aiming to answer the following questions: 1. Why can HIV not replicate in EBV-negative B cells? 2. What does EBV contribute to these cells to enable HIV to replicate? 3. Can HIV infect non-human primate cells, immortalized by EBV? 4. What effects do drugs have on the HIV/EBV interaction? These investigations will teach us more about the biology of HIV and about situations that may occur in AIDS patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI021129-04A1
Application #
3131056
Study Section
(SSS)
Project Start
1987-09-30
Project End
1990-08-31
Budget Start
1987-09-30
Budget End
1988-08-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Medveczky, M M; Geck, P; Vassallo, R et al. (1993) Expression of the collagen-like putative oncoprotein of Herpesvirus saimiri in transformed T cells. Virus Genes 7:349-65
Medveczky, M M; Geck, P; Sullivan, J L et al. (1993) IL-2 independent growth and cytotoxicity of herpesvirus saimiri-infected human CD8 cells and involvement of two open reading frame sequences of the virus. Virology 196:402-12
Mellinghoff, I; Daibata, M; Humphreys, R E et al. (1991) Early events in Epstein-Barr virus genome expression after activation: regulation by second messengers of B cell activation. Virology 185:922-8
Geck, P; Whitaker, S A; Medveczky, M M et al. (1990) Expression of collagenlike sequences by a tumor virus, herpesvirus saimiri. J Virol 64:3509-15
Medveczky, M M; Szomolanyi, E; Hesselton, R et al. (1989) Herpesvirus saimiri strains from three DNA subgroups have different oncogenic potentials in New Zealand white rabbits. J Virol 63:3601-11
Monroe, J E; Calender, A; Mulder, C (1988) Epstein-Barr virus-positive and -negative B-cell lines can be infected with human immunodeficiency virus types 1 and 2. J Virol 62:3497-500
Crumpacker, C; Heagy, W; Bubley, G et al. (1987) Ribavirin treatment of the acquired immunodeficiency syndrome (AIDS) and the acquired-immunodeficiency-syndrome-related complex (ARC). A phase 1 study shows transient clinical improvement associated with suppression of the human immunodeficiency virus and Ann Intern Med 107:664-74
Daum, G S; Sullivan, J L; Ansell, J et al. (1987) Virus-associated hemophagocytic syndrome: identification of an immunoproliferative precursor lesion. Hum Pathol 18:1071-4
Monroe, J E; Andrews, C; Sullivan, J L et al. (1987) Use of cytoplasmic dot-blot hybridization to detect human immunodeficiency virus RNA sequences in cultures of peripheral blood. J Infect Dis 155:320-2
Groopman, J E; Sullivan, J L; Mulder, C et al. (1986) Pathogenesis of B cell lymphoma in a patient with AIDS. Blood 67:612-5