Super Restriction Factors against HIV-1 created from APOBEC3

Thesis (Ph.D.)--University of Washington, 2020The innate immune system provides the first defense against novel pathogens. As a part of the innate immune system, humans encode proteins, called restriction factors, that inhibit replication of viruses like HIV-1. These restriction factors would pose a potent block to HIV-1 viral infection; however, HIV-1 encodes accessory proteins to evade or antagonize the host restriction factors. In this dissertation, I created “super restriction factors,” defined as evolution-guided variants of a natural antiviral protein with improved antiviral activity and resistance to viral antagonism. These super restriction factors provide useful insights about the evolution of host restriction factors and the complex interactions with their viral antagonists as well as a prospective approach to understand cross-species transmission