Abstract

The applicant proposes to understand the role of monocytotropism in primate lentiviral pathogenicity by exploring the following specific aims. 1). Identify physiologic changes in macrophages that are prompted by HIV infection and, in particular how chemokines influence macrophage-lymphocyte interaction; 2). Define the role of viral gene products, especially Nef, in chemokine release, and 3). Examine in vivo and in vitro phenotype of SIV variants containing non-chemokine inducing Nef alleles and of HIV/SIV variants containing Nef/chemokine substitutions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR011589-09
Application #
6641149
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (01))
Program Officer
Robinson, Jerry
Project Start
1995-09-30
Project End
2004-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
9
Fiscal Year
2003
Total Cost
$439,417
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Kaushik, Rajnish; Zhu, Xiaonan; Stranska, Ruzena et al. (2009) A cellular restriction dictates the permissivity of nondividing monocytes/macrophages to lentivirus and gammaretrovirus infection. Cell Host Microbe 6:68-80
Swingler, Simon; Zhou, Jin; Swingler, Catherine et al. (2008) Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe 4:63-76
Sharova, Natalia; Wu, Yuanfei; Zhu, Xiaonan et al. (2008) Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog 4:e1000057
Swingler, Simon; Mann, Angela M; Zhou, Jin et al. (2007) Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. PLoS Pathog 3:1281-90
Sharova, Natalia; Swingler, Catherine; Sharkey, Mark et al. (2005) Macrophages archive HIV-1 virions for dissemination in trans. EMBO J 24:2481-9
Triques, Karine; Stevenson, Mario (2004) Characterization of restrictions to human immunodeficiency virus type 1 infection of monocytes. J Virol 78:5523-7
Somasundaran, Mohan; Sharkey, Mark; Brichacek, Beda et al. (2002) Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Proc Natl Acad Sci U S A 99:9503-8
Briggs, S D; Scholtz, B; Jacque, J M et al. (2001) HIV-1 Nef promotes survival of myeloid cells by a Stat3-dependent pathway. J Biol Chem 276:25605-11
Sharkey, M E; Teo, I; Greenough, T et al. (2000) Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy. Nat Med 6:76-81
Sleigh, R; Sharkey, M; Newman, M A et al. (1998) Differential association of uracil DNA glycosylase with SIVSM Vpr and Vpx proteins. Virology 245:338-43

Showing the most recent 10 out of 12 publications