application) HIV infection in vivo involves many different cell types (uninfected cells permissive for virus replication, infected cells, HIV specific immune cells, and others) that interact with each other and whose numbers, in general, depend on time. The goal of this application is to use mathematical modeling to aid in understanding how such a system can work. The approach is to: i) select mathematical models of HIV/SIV infection based on the criterion that each model's predictions must agree with all significant experimental features of HIV pathogenesis in representative individuals currently available in literature; ii) validate the models selected by finding examples of possible biological mechanisms behind these models; iii) formulate predictions for follow-up experiments to test the models. This """"""""strategy of multiple match"""""""" has been successfully used in the physical sciences for dealing with complex systems of unknown structure, but is novel for HIV research. The investigators will apply this strategy in the two following directions: 1) To elucidate the dominant factors of the virus-T cell interaction in an HIV infection in vivo. 2) To understand the principal factors of HIV evolution in individuals and along the transmission chain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
1K25AI001811-01
Application #
6169459
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Sager, Polly R
Project Start
2000-09-30
Project End
2005-07-31
Budget Start
2000-09-30
Budget End
2001-07-31
Support Year
1
Fiscal Year
2000
Total Cost
$104,026
Indirect Cost
Name
Tufts University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Rouzine, I M; Coffin, J M (2007) Highly fit ancestors of a partly sexual haploid population. Theor Popul Biol 71:239-50
Gheorghiu-Svirschevski, S; Rouzine, I M; Coffin, J M (2007) Increasing sequence correlation limits the efficiency of recombination in a multisite evolution model. Mol Biol Evol 24:574-86
Rouzine, I M; Sergeev, R A; Glushtsov, A I (2006) Two types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus. Proc Natl Acad Sci U S A 103:666-71
Rouzine, I M; Coffin, J M (2005) Evolution of human immunodeficiency virus under selection and weak recombination. Genetics 170:7-18
Rouzine, Igor M; Wakeley, John; Coffin, John M (2003) The solitary wave of asexual evolution. Proc Natl Acad Sci U S A 100:587-92
Rouzine, Igor M; McKenzie, F Ellis (2003) Link between immune response and parasite synchronization in malaria. Proc Natl Acad Sci U S A 100:3473-8
Rouzine, I M; Rodrigo, A; Coffin, J M (2001) Transition between stochastic evolution and deterministic evolution in the presence of selection: general theory and application to virology. Microbiol Mol Biol Rev 65:151-85