Date of Award

2026-05-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Manuel Llano

Abstract

The goal of this work was to characterize the anti-viral role of mouse Schlafen8 and Schlafen9. Expression of these proteins is induced by type I interferon in response to viral infections. Importantly, their human functional orthologs exhibit anti-viral functions, and the structural element required for these activities are conserved in Schlafen8 and Schlafen9. Therefore, it is expected that these proteins will also impair viral replication. An important limitation in this field is that the anti-viral function of human SLFNs has been evidenced only in in vitro cellular models. No informative mutations have been described in human populations so far. Thus, the in vivo relevance of this innate immune system remains to be demonstrated. West Nile virus (WNV) is one of the pathogens antagonized by SLFN11, and a robust mouse model for WNV infection is readily available. Then, this animal model opens the possibility of exploring the anti-viral role of SLFN proteins in vivo. However, the high protein sequence homology of Slfn8 and Slfn9 (85.82% identical) predicts extensive functional redundancy. Then, we decided to determine in in vitro cellular models the anti-viral role of Slfn8 and Slfn9 to inform loss-of-function studies in vivo in a WNV-infection mouse model. Using single-round reporter viruses, we found that Slfn8 and Slfn9 restrict HIV-1 and WNV infection by impairing protein expression. However, Slfn8, but no Slfn9, diminishes the cytopathic effects of WNV replication, suggesting a more important role in the in vivo outcome of this infection. The mechanism implicated in this Slfn8-specific function is unknown yet.

Language

en

Provenance

Received from ProQuest

File Size

44 p.

File Format

application/pdf

Rights Holder

Wendy Paola Alvarez Leal

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