The Role Of Intersubunit Interfaces In HIV-1 Capsid Assembly And Stability

Abstract

This dissertation discusses the role of intersubunit interfaces in HIV-1 capsid assembly and stability. In this study I showed the presence of both the NTD-CTD and CTD-CTD trimer interfaces in mature HIV-1 virions using engineered disulfide crosslinking. Using mutagenesis, I showed that these interfaces are critically important for assembly and stability of the HIV-1 capsid. I also showed that the CTD-CTD trimer interface is formed only after cleavage of CA-SP1. My results provide valuable fundamental knowledge about the biology of capsid assembly and stability and highlight the viral capsid as an attractive target for anti-HIV therapy.