Viruses pose a significant threat to human health based on their ability to cause diseases such as AIDS, influenza, hepatitis, cancer and the common cold. Basic research has revealed much about the molecular details of processes that are essential for viruses to reproduce, but a critical barrier to further progress is a lack of understanding of how factors of the host environment quantitatively impact virus growth. The proposed research aims to address this barrier by advancing new quantitative experiments and computational models of virus growth. The approach will employ, combine and extend perspectives drawn from the fields of experimental evolution and systems biology.
Specific aims of the proposed project will be to: (1) advance computational models of virus growth to provide an integrated dynamic measure of cellular resource use, (2) quantify how resource use is altered during evolutionary adaptation of virus to host cells, and (3) elucidate mechanisms by which viral adaptation alters resource use. The methodology established by this research will set a basis for advancing the development of data-driven predictive models of virus growth. Results of the research will have the potential to significantly impact several fields: the design anti-viral therapeutics, applications of viruses in oncolytic (anti-tumor) cancer therapies, and development of new vaccines. At a more basic level, predictive models of virus growth will be useful for better understanding how viruses grow, evolve and persist in Nature.

Public Health Relevance

Viruses cause a diversity of human diseases including AIDS, influenza, cancer, hepatitis, and the common cold. The proposed research develops new experimental and computational approaches to study and understand how viruses grow. The broad goal of this research is to learn how to better fight diseases caused by viruses. Their work some concerns which serve to spread the enthusiasm somewhat, nevertheless, it came to rest in the exceptional range.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI091646-02
Application #
8204496
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Cassetti, Cristina
Project Start
2010-12-03
Project End
2015-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
Total Cost
$379,546
Indirect Cost
$66,490
Name
University of Wisconsin Madison
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Yin, John; Redovich, Jacob (2018) Kinetic Modeling of Virus Growth in Cells. Microbiol Mol Biol Rev 82:
Morley, Valerie J; Noval, María Gabriela; Chen, Rubing et al. (2018) Chikungunya virus evolution following a large 3'UTR deletion results in host-specific molecular changes in protein-coding regions. Virus Evol 4:vey012
Timm, Andrea C; Warrick, Jay W; Yin, John (2017) Quantitative profiling of innate immune activation by viral infection in single cells. Integr Biol (Camb) 9:782-791
Morley, Valerie J; Turner, Paul E (2017) Dynamics of molecular evolution in RNA virus populations depend on sudden versus gradual environmental change. Evolution 71:872-883
Voigt, Emily A; Swick, Adam; Yin, John (2016) Rapid induction and persistence of paracrine-induced cellular antiviral states arrest viral infection spread in A549 cells. Virology 496:59-66
Warrick, Jay W; Timm, Andrea; Swick, Adam et al. (2016) Tools for Single-Cell Kinetic Analysis of Virus-Host Interactions. PLoS One 11:e0145081
Akpinar, Fulya; Inankur, Bahar; Yin, John (2016) Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell. J Virol 90:7552-7566
Wasik, Brian R; Muñoz-Rojas, Andrés R; Okamoto, Kenichi W et al. (2016) Generalized selection to overcome innate immunity selects for host breadth in an RNA virus. Evolution 70:270-81
Gloria-Soria, A; Kellner, D A; Brown, J E et al. (2016) Temporal genetic stability of Stegomyia aegypti (= Aedes aegypti) populations. Med Vet Entomol 30:235-40
Williams, Elizabeth S C P; Morales, Nadya M; Wasik, Brian R et al. (2016) Repeatable Population Dynamics among Vesicular Stomatitis Virus Lineages Evolved under High Co-infection. Front Microbiol 7:370

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