EAPSI: Modeling virus protein shell assembly

Sadre-Marandi Farrah, Fort Collins CO

Investigators

Abstract

This proposed research project aims to examine the human immunodeficiency virus type 1 (HIV-1). Mathematical models will be developed specifically for the first stage of the virus formation, called the nucleation stage, of HIV-1 capsid. The capsid acts as a protective shell for the genetic material (DNA or RNA) inside the virus and is in its weakest stage during maturation. After the capsid matures, the virus is able to attack new cells and replicate its DNA or RNA, leading to virus spread throughout the body. Therefore it is of great interest to characterize the favorable, restrictive, or even prohibitive conditions for capsid development so that these deterministic features can be targeted with antiviral therapies. This research will be conducted in collaboration with the computational virology expertise of Dr. Xiufen Zou at Wuhan University in China and will be validated with biological experiment data using the resources from The (China) State Key Laboratory of Virology. Previous work has modeled the process of viral capsid assembly using one large-size dynamical system, combining both the nucleation and elongation phase. This approach has overlooked the effects and experimental evidence of these two stages. Investigating the nucleation stage first gives this model a unique advantage for characterizing the conditions required to start capsid formation and produce the building blocks for the mature capsid. Numerical simulations of the capsid protein assembly will be conducted using a 6-species dynamical systems model and will be implemented as a simulation code package. Deterministic and stochastic factors in the biological processes of viral capsid assembly will be examined as well as the stability of equilibria and sensitivity to model parameters. While in vitro experiments can be conducted to investigate these conditions, certain biological parameters in this process are immensely difficult to measure, so the mathematical model will enable us to analyze sensitivity of these parameters to outside factors, such as drug treatments. This NSF EAPSI award is funded in collaboration with the Chinese Ministry of Science and Technology.