Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 4 of 4
Full-Text Articles in Life Sciences
Characterizing The Interaction Between Human Adenovirus E1a And Sting, Jessica Hill
Characterizing The Interaction Between Human Adenovirus E1a And Sting, Jessica Hill
Electronic Thesis and Dissertation Repository
When challenged by viral DNA, the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS) signals through the adaptor protein stimulator of interferon genes (STING) to induce a primary type I IFN response. Studies from recent years have also revealed shared architecture between metabolism and innate immunity. Viruses have evolved to counteract these mechanisms. Human adenovirus (HAdV) early region 1A (E1A) protein antagonizes the cGAS-STING pathway to prevent an innate immune response by physically interacting with STING. I hypothesize that the interaction between E1A and STING is mediated through several motifs and involves ribosomal protein S6 kinase beta-1 (S6K1). Using a series …
Evolutionary And In Silico Analysis Of The Antiviral Trim22 Gene, Jenna Kelly
Evolutionary And In Silico Analysis Of The Antiviral Trim22 Gene, Jenna Kelly
Electronic Thesis and Dissertation Repository
Tripartite motif protein 22 (TRIM22) is an evolutionarily ancient interferon-induced protein that been shown to potently inhibit human immunodeficiency virus (HIV), hepatitis B virus (HBV), and influenza A virus (IAV) replication. Altered TRIM22 expression levels have also been linked to autoimmune disease, cancer, and cellular proliferation. Despite its important role in a number of biological processes, the factors that influence TRIM22 expression and/or antiviral activity remain largely unknown. To identify key functional sites in TRIM22, we performed extensive evolutionary and in silico analyses on the TRIM22 coding region. These tools allowed us to pinpoint multiple sites in TRIM22 that have …
Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca
Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca
Electronic Thesis and Dissertation Repository
Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to monoubiquitinate …
Restriction Of Hiv-1 Replication By Unique Trim22 Isoforms., Clayton Hattlmann
Restriction Of Hiv-1 Replication By Unique Trim22 Isoforms., Clayton Hattlmann
Electronic Thesis and Dissertation Repository
Understanding how the immune system reacts to HIV infection and why normal antiviral defenses are insufficient to fight infection is a key step towards creating better therapies. Several interferon-induced proteins, such as the tripartite motif protein TRIM22, are capable of restricting HIV-1 replication; however single nucleotide polymorphisms (SNPs) can dramatically impact the actions of these proteins. While the trim22 gene contains numerous SNPs, no study has addressed how these may affect TRIM22 functions. Here we provide the first direct comparison of two TRIM22 unique isoforms. Through confocal microscopy we observed these isoforms exhibit different patterns of localization. In vitro studies …