Abstract

The principal aim is to use rhesus macaques infected intravaginally with SIV as a model for HIV-1 transmission and a foundation of designing and evaluating vaccine candidates. Virus-cell relationships will be defined by in situ hybridization and PCR-based techniques and the cellular immune response will be identified and quantified. The proposal involves a consortium of investigators headed by Ashley Haase and includes Christopher Miller, David Watkins and Steven Wolinsky.
In aim 1, two competing hypotheses will be tested following transmission: SIV replication is confined to the portal of entry for a sufficient time to allow an anamnestic immune defense to prevent dissemination vs. transmission leads to unimpeded spread in DCs and/or macrophages beyond the site of entry.
In aim 2, they will examine the hypothesis that latently or chronically infected cells arise quickly after transmission.
In aim 3, they will test the hypothesis that the balance between virus reproduction and the scope and breadth of the immune response determines the success or failure of establishing a persistent infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048484-03
Application #
6534300
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (03))
Program Officer
Sharma, Opendra K
Project Start
2000-09-01
Project End
2004-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$897,733
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Estes, Jacob D; Reilly, Cavan; Trubey, Charles M et al. (2015) Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy. J Infect Dis 211:744-54
Zeng, Ming; Paiardini, Mirko; Engram, Jessica C et al. (2012) Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution. Blood 120:1856-67
Zeng, Ming; Haase, Ashley T; Schacker, Timothy W (2012) Lymphoid tissue structure and HIV-1 infection: life or death for T cells. Trends Immunol 33:306-14
Zeng, Ming; Southern, Peter J; Reilly, Cavan S et al. (2012) Lymphoid tissue damage in HIV-1 infection depletes naive T cells and limits T cell reconstitution after antiretroviral therapy. PLoS Pathog 8:e1002437
Zeng, Ming; Smith, Anthony J; Wietgrefe, Stephen W et al. (2011) Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J Clin Invest 121:998-1008
Haase, Ashley T (2010) Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464:217-23
Bosinger, Steven E; Li, Qingsheng; Gordon, Shari N et al. (2009) Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 119:3556-72
Li, Qingsheng; Skinner, Pamela J; Ha, Sang-Jun et al. (2009) Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science 323:1726-9
Li, Qingsheng; Skinner, Pamela J; Duan, Lijie et al. (2009) A technique to simultaneously visualize virus-specific CD8+ T cells and virus-infected cells in situ. J Vis Exp :
Estes, Jacob D; Haase, Ashley T; Schacker, Timothy W (2008) The role of collagen deposition in depleting CD4+ T cells and limiting reconstitution in HIV-1 and SIV infections through damage to the secondary lymphoid organ niche. Semin Immunol 20:181-6

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