The enzyme Sialic acid acetylesterase maintains peripheral B cell tolerance and prevents the activation of B cells that see self antigens weakly. This enzyme is of relevance in both murine and human B cells. Inhibiting this esterase may permit the activation of B cells that see conserved but weak epitopes on HIV gp120. The SIAE gene will be knocked down in humanized mice. Both SIAE knockdown humanized mice and Siae mutant conventional mice will be immunized with gp140 trimers in an attempt to ask if inhibition of SIAE favors the generation of neutralizing antibodies against HIV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI090867-03
Application #
8291408
Study Section
Special Emphasis Panel (ZAI1-BP-A (M2))
Program Officer
Malaspina, Angela
Project Start
2010-06-15
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$904,644
Indirect Cost
$341,783
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Kalay, Ersan; Sezgin, Orhan; Chellappa, Vasant et al. (2012) Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome. Am J Hum Genet 90:76-85
Pillai, Shiv; Mattoo, Hamid; Cariappa, Annaiah (2011) B cells and autoimmunity. Curr Opin Immunol 23:721-31