Individual variations in immune status and function determine responses to infection and contribute to disease severity and outcome. In this proposal, we will employ recent advances in high-throughput technology to profile individual immune responses to identify the molecular signatures defining individual immune responses to flaviviral infections. We will investigate the immune responses of patients from stratified cohorts using as models West Nile virus (WNV), generally a transient infection, and hepatitis C virus (HCV), which can be transient with a resolving viremia, or chronic with a persistent viremia leading to cirrhosis and death. Using highly sensitive multidimensional cell flow cytometry, multiplexed gene expression analysis, and correlation with clinical history, we will provide molecular profiles of cellular mechanisms of primary human immune cells. The profiling studies of Aims 1 and 2 will form the basis for modeling and predictions of networks and critical cellular pathways to identify key effectors and regulatory mechanisms of resistance to flaviviral infections (see Research Project 3). These predictions will be validated through detailed examination in primary cells to demonstrate the role of identified components.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089992-04
Application #
8495897
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$390,740
Indirect Cost
$120,281
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Murray, Kristy O; Nolan, Melissa S; Ronca, Shannon E et al. (2018) The Neurocognitive and MRI Outcomes of West Nile Virus Infection: Preliminary Analysis Using an External Control Group. Front Neurol 9:111
Molony, Ryan D; Malawista, Anna; Montgomery, Ruth R (2018) Reduced dynamic range of antiviral innate immune responses in aging. Exp Gerontol 107:130-135
Martin-Gayo, Enrique; Cole, Michael B; Kolb, Kellie E et al. (2018) A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers. Genome Biol 19:10
Wang, Xiaomei; Malawista, Anna; Qian, Feng et al. (2018) Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes. Oncotarget 9:9572-9580
Cahill, Megan E; Conley, Samantha; DeWan, Andrew T et al. (2018) Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis. BMC Infect Dis 18:282
van Dijk, David; Sharma, Roshan; Nainys, Juozas et al. (2018) Recovering Gene Interactions from Single-Cell Data Using Data Diffusion. Cell 174:716-729.e27
Ordovas-Montanes, Jose; Dwyer, Daniel F; Nyquist, Sarah K et al. (2018) Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560:649-654
Mead, Benjamin E; Ordovas-Montanes, Jose; Braun, Alexandra P et al. (2018) Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol 16:62
Avey, Stefan; Mohanty, Subhasis; Wilson, Jean et al. (2017) Multiple network-constrained regressions expand insights into influenza vaccination responses. Bioinformatics 33:i208-i216
Cahill, Megan E; Yao, Yi; Nock, David et al. (2017) West Nile Virus Seroprevalence, Connecticut, USA, 2000-2014. Emerg Infect Dis 23:708-710

Showing the most recent 10 out of 64 publications