Abstract

Through comparative analysis, different coronaviruses, including the novel SARS-CoV-2 and human seasonal coronaviruses hCoV-OC43 and hCoV-NL63 will be used to unveil both their similarities and differences in cellular susceptibility and permissiveness, innate immune responses, and immune modulatory potential in primary human cell systems including monocyte derived dendritic cells (MDDCs), normal human bronchial epithelial cells (NHBEs), and an ex vivo tonsil histoculture (HC) system. We will use state of the art techniques to analyze tose responses intracellularly and extracellularly. Our group specializes in the manipulation of primary human cell systems and investigating both innate immune responses to viral infection as well as viral antagonism of innate immune sensing. As such we are uniquely positioned to respond to this new public health threat and provide critical information regarding the molecular biology of SARS-CoV-2.

Public Health Relevance

In this proposal we will analyze the early and late immune responses induced by human coronaviruses, including the new SARS-CoV-2 in primary human systems. Using state of the art immunological and biological techniques we will investigate the strategies of immune evasion used by different coronaviruses at the cellular level. The data generated in this proposal will inform on vaccine and antiviral drug design for human coronaviruses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI118610-06S2
Application #
10157384
Study Section
Program Officer
Kelly, Halonna R
Project Start
2020-06-08
Project End
2021-05-31
Budget Start
2020-06-08
Budget End
2021-05-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Manganaro, Lara; Hong, Patrick; Hernandez, Matthew M et al. (2018) IL-15 regulates susceptibility of CD4+ T cells to HIV infection. Proc Natl Acad Sci U S A 115:E9659-E9667
Andrade, Paulina; Coloma, Josefina; Harris, Eva (2018) ELISPOT-Based ""Multi-Color FluoroSpot"" to Study Type-Specific and Cross-Reactive Responses in Memory B Cells after Dengue and Zika Virus Infections. Methods Mol Biol 1808:151-163
Wang, Daifeng; Liu, Shuang; Warrell, Jonathan et al. (2018) Comprehensive functional genomic resource and integrative model for the human brain. Science 362:
Michlmayr, Daniela; Pak, Theodore R; Rahman, Adeeb H et al. (2018) Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases. Mol Syst Biol 14:e7862
Tsai, Wen-Yang; Youn, Han Ha; Tyson, Jasmine et al. (2018) Use of Urea Wash ELISA to Distinguish Zika and Dengue Virus Infections. Emerg Infect Dis 24:1355-1359
Young, George R; Terry, Sandra N; Manganaro, Lara et al. (2018) HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements. J Virol 92:
Tan, Yi; Pickett, Brett E; Shrivastava, Susmita et al. (2018) Differing epidemiological dynamics of Chikungunya virus in the Americas during the 2014-2015 epidemic. PLoS Negl Trop Dis 12:e0006670
Lin, Luan; Chen, Quan; Hirsch, Jeanne P et al. (2018) Temporal genetic association and temporal genetic causality methods for dissecting complex networks. Nat Commun 9:3980
Amir, El-Ad David; Guo, Xinzheng V; Mayovska, Oksana et al. (2018) Average Overlap Frequency: A simple metric to evaluate staining quality and community identification in high dimensional mass cytometry experiments. J Immunol Methods 453:20-29
Premkumar, Lakshmanane; Collins, Matthew; Graham, Stephen et al. (2018) Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection. J Clin Microbiol 56:

Showing the most recent 10 out of 42 publications