Document Type

Honors Thesis

Publication Date

Spring 2014

Abstract

The TNFAIP8 gene family is a recently discovered family of immune-related genes that have been implicated in both innate immunity and immune homeostasis. This gene family consists of tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8), TNFAIP8L1 (TIPE1), TNFAIP8L2 (TIPE2), and TNFAIP8L3 (TIPE3), of which only two, TNFAIP8 and TIPE2, have been characterized. Previous studies have revealed high sequence homology among family members, as is evident in the collective involvement of TNFIAP8 and TIPE2 in critical immune-related diseases, including cancer and inflammatory disease, respectively. However, TIPE1 has been left relatively uncharacterized, and its role in the context of antiviral innate immunity has largely been unexplored.

Using RAW264.7 macrophages as an in vitro model and the zebrafish, Danio rerio, as an in vivo model, we hope to elucidate the antiviral innate immune function of TIPE1. Morpholino-mediated TIPE1 knockdown resulted in decreased zebrafish survival upon influenza infection, suggesting that TIPE1 is a critical antiviral gene. Additionally, through stimulation of certain antiviral pathways in vitro, and subsequent real-time quantitative polymerase chain reaction (RT-qPCR), preliminary data has revealed a possible inhibitory immune role for TIPE1.

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