CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics

About CHEETAH

To initiate an infection, HIV-1 must complete a series of transformations that include fusing with the target cell membrane, releasing the viral core particle into the cytoplasm where it begins to reverse transcribe the viral RNA into DNA and moves into the nucleus, losing the external capsid (termed “uncoating”), and integrating the viral DNA genome into the host chromosome. These early steps in HIV-1 replication can be challenging to study because infections are initiated by single virions, and because many of the key transformations occur deep within the cell. Project 1 is focused on uncovering the molecular mechanisms that underlie these key processes in the first half of the viral life cycle (yellow boxes).


Although HIV-1 ultimately gains the upper hand in untreated infections, human cells are not defenseless victims, but rather can sense and inhibit HIV-1 infections using a series of powerful innate immune responses. Nearly every step in the first half of the HIV-1 life cycle has a corresponding innate immune sensing or restriction activity, and defining these processes in molecular detail is the focus of our studies in Project 2 (rose boxes). Our Center will gain great synergy from the interplay between our studies of viral processes and their counteracting restriction mechanisms.

Complex biological processes like HIV/AIDS can only be truly be understood by considering all possible resolution scales, from the molecular, through the cellular, to the organismal level. Studies in Project 3 are designed to create and apply approaches for studying and modulating viral dynamics, latency, and rebound across resolution scales, and to leverage advances in molecular virology and protein design to create new broad-acting antiviral systems and virus-inspired delivery systems (blue boxes). In essence, our goal is to create the foundations necessary to tackle new frontiers in HIV-1 biology and medicine, including the development of cure strategies, broad antiviral therapeutics, and methods for delivering biologic therapeutics efficiently into specific cell types.