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Theoretical and Computational Biophysics Group - "The HIV-1 capsid and its interactions with host cell factors."

Event Type
Klaus Schulten - TCB Group
3269 Beckman Institute
Feb 3, 2014   3:00 pm  
Dr. Juan Perilla, TCB Group, UIUC
Nancy Mallon
Originating Calendar
Physics - Theoretical Biophysics Seminar

The family of Retroviruses are characterized by their ability to incorporate viral DNA into a host cell's genome. Most retroviruses infect cells during mitosis, when the chromatin is exposed to the cytoplasm. Conversely, the genus of Lentiviruses, like the human immunodeficiency virus (HIV), have evolved in order to infect non-dividing cells. Since the host cell's chromatin is protected by the nucleus, the HIV infection process requires coordination between  reverse transcription of viral RNA and nuclear import. Viral RNA is encased in a shell of the capsid protein CA. Originally thought to play a trivial role in the infection process, it is now well established that the viral capsid fulfills several essential functions. In particular, capsid involvement in the prevention of innate sensor triggering, regulation of reverse transcription, and regulation of the nuclear import pathway is of central importance to the successful infection of a host cell. Interestingly, all of these functions seem to be highly dependent on interactions between the capsid and Cyclophilin-A. In this talk I will present the structure of the HIV-1 capsid as derived from a synergy of experimental and computational techniques, as well as its physical properties obtained from Molecular Dynamics simulations. Additionally, I will present the interactions between the capsid and Cyclophilin-A based on new experimental and computational measurements as well as their implications in the infection cycle. Finally, in light of these new developments, we address the interactions between therapeutic small molecules and the capsid.

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