We propose a systematic proteomic analysis of the human innate immune response to DNA infection coupled with a functional analysis of genes in the network. We focus on the signaling pathways involved in transcription of type I interferon. This project provides a glimpse into the global architecture of antiviral signaling and serves as a resource for further mechanistic analysis of the pathway.

Public Health Relevance

: The molecular mechanisms involved in regulating innate immune responses to DNA viruses are incompletely understood. We propose a systematic proteomic approach to discover the molecular signaling pathways controlling responses to DNA and DNA viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI099860-01
Application #
8283811
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Palker, Thomas J
Project Start
2012-02-15
Project End
2014-01-31
Budget Start
2012-02-15
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$254,250
Indirect Cost
$104,250
Name
Harvard University
Department
Pathology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Fu, Bishi; Wang, Lingyan; Ding, Hao et al. (2015) TRIM32 Senses and Restricts Influenza A Virus by Ubiquitination of PB1 Polymerase. PLoS Pathog 11:e1004960
Li, Shitao; Wang, Lingyan; Fu, Bishi et al. (2014) Trim65: a cofactor for regulation of the microRNA pathway. RNA Biol 11:1113-21
Li, Shitao; Wang, Lingyan; Fu, Bishi et al. (2014) TRIM65 regulates microRNA activity by ubiquitination of TNRC6. Proc Natl Acad Sci U S A 111:6970-5
Fu, Bishi; Li, Shitao; Wang, Lingyan et al. (2014) The ubiquitin conjugating enzyme UBE2L3 regulates TNF?-induced linear ubiquitination. Cell Res 24:376-9
Wang, Lingyan; Li, Shitao; Dorf, Martin E (2012) NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses. PLoS One 7:e43756