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Towards the Elucidation of Novel Viral Factors that Hijack Host Ubiquitination Pathways
Author(s) -
Lippa Geoffrey Michael,
Muehl Madison,
Lapham Joshua
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.461.12
Subject(s) - ubiquitin , biology , cullin , viral replication , viral structural protein , microbiology and biotechnology , ubiquitin ligase , ubiquitin protein ligases , signal transducing adaptor protein , viral protein , scaffold protein , viral entry , viral pathogenesis , transcription factor , virus , protein degradation , virology , signal transduction , genetics , gene
Viruses, like human immunodeficiency virus (HIV), have the ability to hijack host pathways to promote disease pathogenesis. The process of ubiquitination is used by the cell for regulating signal transduction, DNA replication, cellular development, transcription, and the cell cycle. Ubiquitination and the proteasome work together to degrade a variety of cellular target proteins involved in the processes described. The covalent attachment of a ubiquitin protein to a cellular substrate requires a multi‐protein complex consisting of a scaffold protein, adaptor module, substrate receptor, RING protein, and E2 protein. In HIV, the Cullin‐RING E3 ligase complex utilizing Cullin5, Rbx2, E2, Elongin B, Elongin C, and Vif (viral infectivity factor), amongst other accessory proteins results in the targeted degradation of antiretroviral factor APOBEC3G. Other viruses have followed suit countering these natural processes by expressing viral proteins capable of sequestering or enhancing host ubiquitination conducted by CRL complexes. Research efforts have been made in discovering both host proteins targeted in this fashion and those viral proteins responsible for this aberrant activity. Through bioinformatics and structural analysis new potential viral proteins involved in the above CRL complex have been discovered. These targets are predicted to play a role in viral fitness for Hepatitis C virus (NS5A), West Nile Virus (NS1), and Lassa virus (Z‐protein) due to their similarities with the host substrate receptor SOCS2. We are currently in the process of co‐expressing parts of the CRL complex with these viral targets in E. coli with the goal of evaluating their interactions. Utilizing in vitro pull‐down assays and thermodynamic techniques we hope to verify the viral proteins involved in the CRL complex and their mechanisms of interaction laying the groundwork for new avenues of anti‐viral therapeutics. Support or Funding Information Funding was achieved through Alfred Research Grants for Undergraduate Research. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .