Date of Award
Doctor of Philosophy
The Schlafen (SLFN) family of proteins are known for being encoded by interferon stimulated genes. The family is divided into three groups (I, II, III), for which the largest in size belong to the subgroup III. In humans, group III has the most members (SLFN5, SLFN11, SLFN13 and SLFN14); there is no member of group I and only one member of group II (SLFN12). All human SLFNs belonging to group III have been reported to impair viral protein expression or infection across a variety of viruses. The antiviral function is mediated in SLFN11 and SLFN13 by their tRNase activity, and in the catalytically inactive SLFN5 by its DNA binding properties. The mechanism of SLFN14 to impair the expression of viral proteins is unknown. In contrast to human SLFNs, the antiviral activity of murine SLFN group III, including SLFN5, SLFN8, SLFN9 and SLFN14, has not been reported. In my thesis work I have advanced our knowledge of this family. I studied the antiviral activity of SLFNs using as models West Nile virus (WNV) and HIV-1. I identified a major role of SLFN14 in regulating at the translational level the expression of HIV-1 viral proteins encoded by codon-biased mRNAs. In addition, I discovered that SLFN11 and SLFN13, and their mouse orthologs SLFN9 and SLFN8, inhibit HIV-1 protein expression by a codon-biased mechanism, whereas SLFN11 and SLFN9, but not SLFN8, impairs WNV replication. Furthermore, I identified the nuclear localization signals that drive nuclear localization of SLFN11, and the role of proteolysis in the regulation of levels of SLFN13 and SLFN14.
Recieved from ProQuest
Carlos A Valenzuela
Valenzuela, Carlos A., "Functional Characterization Of The Human And Murine Schlafen Family Group Iii" (2023). Open Access Theses & Dissertations. 4029.