Abstract

The objectives of this proposal are to examine the effect of viral infection on macrophages in greater detail, using the alveolar macrophage and SIV as a basis of study. Specifically, the aims of this proposal are to: 1) to study the microenvironmental influences of cytokines and activation agents on the efficiency of viral replication within SIV-infected alveolar macrophages, 2) to study the function of SIV-infected alveolar macrophages, as determined by their ability to present antigen and participate in autologous mixed lymphocyte reactions, ability to phagocytize and kill bacteria, ability to perform cytotoxic functions against neoplastic and parasitic targets, and the ability to produce cytokines and immunoregulatory molecules upon stimulation, 3) study any alterations in macrophage-related gene expression resulting from SIV infection and investigate the molecular basis for these alterations, 4) study the in vivo significance of macrophage tropism by comparing the pathogenic potential of SIV isolates that propagate well within macrophages in vitro with isolates that do not grow at all within this particular cell, and 5) investigate the molecular determinants responsible for the growth of SIV within macrophages.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029855-03
Application #
3144793
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1990-03-01
Project End
1995-02-28
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Mansfield, K G; Pauley, D; Young, H L et al. (1995) Mycobacterium avium complex in macaques with AIDS is associated with a specific strain of simian immunodeficiency virus and prolonged survival after primary infection. J Infect Dis 172:1149-52
Silber, A; Newman, W; Sasseville, V G et al. (1994) Recruitment of lymphocytes during cutaneous delayed hypersensitivity in nonhuman primates is dependent on E-selectin and vascular cell adhesion molecule 1. J Clin Invest 93:1554-63
Sasseville, V G; Newman, W; Brodie, S J et al. (1994) Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions. Am J Pathol 144:27-40
Brodie, S J; Sasseville, V G; Reimann, K A et al. (1994) Macrophage function in simian AIDS. Killing defects in vivo are independent of macrophage infection, associated with alterations in Th phenotype, and reversible with IFN-gamma. J Immunol 153:5790-801
Horvath, C J; Hunt, R D; Simon, M A et al. (1993) An immunohistologic study of granulomatous inflammation in SIV-infected rhesus monkeys. J Leukoc Biol 53:532-40
Mori, K; Ringler, D J; Desrosiers, R C (1993) Restricted replication of simian immunodeficiency virus strain 239 in macrophages is determined by env but is not due to restricted entry. J Virol 67:2807-14
Horvath, C J; Simon, M A; Bergsagel, D J et al. (1992) Simian virus 40-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome. Am J Pathol 140:1431-40
Sasseville, V G; Newman, W A; Lackner, A A et al. (1992) Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus. Am J Pathol 141:1021-30
Simon, M A; Chalifoux, L V; Ringler, D J (1992) Pathologic features of SIV-induced disease and the association of macrophage infection with disease evolution. AIDS Res Hum Retroviruses 8:327-37
Mori, K; Ringler, D J; Kodama, T et al. (1992) Complex determinants of macrophage tropism in env of simian immunodeficiency virus. J Virol 66:2067-75

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