Abstract

The goal of these studies is to characterize the role played by HIV and SIV co-receptors in virus entry, and the impact that this has on viral transmission and disease progression. In the first specific aim, proven techniques will be used to identify new co-receptors from lymphoid and non-lymphoid tissue and to characterize what strains of HIV and SIV are able to use these receptors. The second specific aim is to identify why CCR5 is non-functional for entry when expressed on murine T-cells, despite functioning when expressed on murine fibroblasts. The third specific aim is to determine why mutant HUT78 cells that express CD4 and CXCR4 are non-permissive for HIV entry or env-mediated membrane fusion. The fourth specific aim is to characterize regions of CD4 that interact with CCR5 and that are involved in the HIV entry process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI033303-09
Application #
6124265
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Plaeger, Susan F
Project Start
1992-12-01
Project End
2002-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
9
Fiscal Year
2000
Total Cost
$522,676
Indirect Cost

  Institution

Name
New York University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016

  Publications

Lee, KyeongEun; Ambrose, Zandrea; Martin, Thomas D et al. (2010) Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 7:221-33
Browne, Edward P; Littman, Dan R (2009) Myd88 is required for an antibody response to retroviral infection. PLoS Pathog 5:e1000298
Manel, Nicolas; Unutmaz, Derya; Littman, Dan R (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9:641-9
Browne, Edward P; Littman, Dan R (2008) Species-specific restriction of apobec3-mediated hypermutation. J Virol 82:1305-13
Zhang, Jing-xin; Diehl, Gretchen E; Littman, Dan R (2008) Relief of preintegration inhibition and characterization of additional blocks for HIV replication in primary mouse T cells. PLoS One 3:e2035
Srivastava, Smita; Swanson, Selene K; Manel, Nicolas et al. (2008) Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog 4:e1000059
Soos, T J; Sims, T N; Barisoni, L et al. (2006) CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney. Kidney Int 70:591-6
Hill, C M; Kwon, D; Jones, M et al. (1998) The amino terminus of human CCR5 is required for its function as a receptor for diverse human and simian immunodeficiency virus envelope glycoproteins. Virology 248:357-71
Hill, C M; Deng, H; Unutmaz, D et al. (1997) Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J Virol 71:6296-304
Weiss, C D; Barnett, S W; Cacalano, N et al. (1996) Studies of HIV-1 envelope glycoprotein-mediated fusion using a simple fluorescence assay. AIDS 10:241-6