CD8+ Cell Noncytolytic Inhibition of HIV-1

Tomaras, Georgia Doris

Abstract

The PI proposes experiments to understand the noncytolytic inhibition of HIV mediated by CD8+ T cells. The goals are to: a) identify the factors, b) define the mechanisms, c) identify viral determinants which allow susceptibility. The PI will study whether inhibition occurs at integration or inhibition of expression. He also will characterize the factors from the Herpes-virus saimiri line that he has developed and examine the chemokines recently reported to be involved. The overall goal is to understand the basis for CD8 HIV inhibitory activity and may facilitate therapies for HIV.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Project (R01)
• Project #: 5R01AI040017-05
• Application #: 6169954
• Study Section: AIDS and Related Research Study Section 3 (ARRC)
• Program Officer: Bridges, Sandra H
• Project Start: 1996-07-01
• Project End: 2002-05-31
• Budget Start: 2000-06-01
• Budget End: 2002-05-31
• Support Year: 5
• Fiscal Year: 2000
• Total Cost: $280,436

Institution

• Name: Duke University
• Department: Surgery
• Type: Schools of Medicine
• DUNS #: 044387793
• City: Durham
• State: NC
• Country: United States
• Zip Code: 27705

Publications

Tomaras, G D; Greenberg, M L (2001) CD8+ T cell mediated noncytolytic inhibition of human immunodeficiency virus type I. Front Biosci 6:D575-98

Cleghorn, F R; Jack, N; Carr, J K et al. (2000) A distinctive clade B HIV type 1 is heterosexually transmitted in Trinidad and Tobago. Proc Natl Acad Sci U S A 97:10532-7

Tomaras, G D; Lacey, S F; McDanal, C B et al. (2000) CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression. Proc Natl Acad Sci U S A 97:3503-8

Hu, Q; Trent, J O; Tomaras, G D et al. (2000) Identification of ENV determinants in V3 that influence the molecular anatomy of CCR5 utilization. J Mol Biol 302:359-75

Hu, Q X; Barry, A P; Wang, Z X et al. (2000) Evolution of the human immunodeficiency virus type 1 envelope during infection reveals molecular corollaries of specificity for coreceptor utilization and AIDS pathogenesis. J Virol 74:11858-72

Lacey, S F; Weinhold, K J; Chen, C H et al. (1998) Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes from an HIV type 1-infected asymptomatic individual. AIDS Res Hum Retroviruses 14:521-31

Lacey, S F; McDanal, C B; Horuk, R et al. (1997) The CXC chemokine stromal cell-derived factor 1 is not responsible for CD8+ T cell suppression of syncytia-inducing strains of HIV-1. Proc Natl Acad Sci U S A 94:9842-7