The type I interferon (IFN) system represents one of the first-line defenses against viral infections. However, viral pathogens have evolutionarily acquired different exquisite mechanisms to counteract the IFN system of the host. Viral-encoded IFN antagonists have been identified among most groups of viruses. Since targeted deletion of the viral IFN antagonist genes results in viral attenuation, these genes represent major virulence factors. Human respiratory syncytial virus (RSV) is the leading cause of severe viral respiratory infections in infants and young children. Although recent evidence suggests that RSV infection results in inhibition of the antiviral action of IFN, little is known on the molecular mechanisms responsible for the RSV resistance to the IFN system. We have identified the NS2 protein of RSV as an RSV-encoded IFN antagonist based on its ability to restore the replication of an IFN-sensitive virus. In this part of the program project we will focus on the mechanism of evasion of the IFN system by RSV and its contribution to RSV replication, with special focus on the role of the NS2 protein. Through our studies, we will gain insights on the interactions between the NS2 protein of RSV and IFN-regulated pathways in the host. Such interactions might be good targets for antiviral and/or vaccine approaches against this important human pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI052106-01
Application #
6575549
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Li, Jiangning; Campbell, Jean S; Mitchell, Claudia et al. (2009) Relationships between deficits in tissue mass and transcriptional programs after partial hepatectomy in mice. Am J Pathol 175:947-57
Chu, Vu T; Gottardo, Raphael; Raftery, Adrian E et al. (2008) MeV+R: using MeV as a graphical user interface for Bioconductor applications in microarray analysis. Genome Biol 9:R118
Kotla, Swathi; Peng, Tao; Bumgarner, Roger E et al. (2008) Attenuation of the type I interferon response in cells infected with human rhinovirus. Virology 374:399-410
Katze, Michael G; Fornek, Jamie L; Palermo, Robert E et al. (2008) Innate immune modulation by RNA viruses: emerging insights from functional genomics. Nat Rev Immunol 8:644-54
Peng, Tao; Zhu, Jia; Hwangbo, Yon et al. (2008) Independent and cooperative antiviral actions of beta interferon and gamma interferon against herpes simplex virus replication in primary human fibroblasts. J Virol 82:1934-45
Katze, Michael G; Korth, Marcus J (2007) Lost in the world of functional genomics, systems biology, and translational research: is there life after the Milstein award? Cytokine Growth Factor Rev 18:441-50
Fornek, Jamie L; Korth, Marcus J; Katze, Michael G (2007) Use of functional genomics to understand influenza-host interactions. Adv Virus Res 70:81-100
Roth-Cross, Jessica K; Martinez-Sobrido, Luis; Scott, Erin P et al. (2007) Inhibition of the alpha/beta interferon response by mouse hepatitis virus at multiple levels. J Virol 81:7189-99
Gottardo, Raphael; Raftery, Adrian E; Yeung, Ka Yee et al. (2006) Bayesian robust inference for differential gene expression in microarrays with multiple samples. Biometrics 62:10-8
Palese, Peter; Tumpey, Terrence M; Garcia-Sastre, Adolfo (2006) What can we learn from reconstructing the extinct 1918 pandemic influenza virus? Immunity 24:121-4

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