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Higher animals possess a powerful arsenal of immune responses that are able to remove or deplete almost any invading pathogen to undetectable levels. In the case of HIV, immune responses can only curb replication of the virus, but not clear it altogether. The key players in the HIV control are cytotoxic CD8 T lymphocytes (CTLs) that recognize and kill infected cells, and helper CD4 T cells that regulate CTL response. A likely cause of HIV persistence is infection of helper cells by the virus, which eventually culminates in AIDS. Yet, before symptoms emerge, approximate balance between replication and death of every relevant cell type is maintained for years.
One direction of our project is interaction between HIV and the immune system. In the spirit of systems biology, I am using various data on kinetics of immune cells to develop, by consecutive iterations, a realistic model. The method sheds light on the order of cell differentiation, including cells permissive for virus replication, infected cells, CTLs, and helper cells, and the way these cell compartments interact.
Rapid genetic evolution of HIV in infected individuals adds another sinister twist to the story: the virus becomes resistant to replication inhibitor drugs and escapes from vaccine -induced immune response. An HIV genome has hundreds of sites that adapt rapidly to variety of host conditions, including currently used replication inhibitors or immune response. A factor that greatly accelerates the process is recombination between viruses co-infecting the same cell, existing in addition to simple copying of paternal genomes. Hence, the second task is to develop mathematical theory of many-site evolution in the presence of recombination, selection, and genetic drift. Apart from the obvious biomedical implications, these studies help to understand how asexual reproduction evolved to a higher, sexual form. Other organisms that chose to reproduce in such a partly sexual fashion include coral, yeast, some fish, and plants. |
