Viruses are pathogenic agents
which affect all varieties of organisms, including plants, animals and humans.
These microscopic particles are genetically simple organisms which encode a
limited number of proteins that undertake a wide range of functions. While
structurally distinct, viruses often share common characteristics that have
evolved to aid in their infectious life cycles. A commonly underappreciated
characteristic of many deadly viruses is a lipid envelope coat that surrounds
them. Lipid enveloped viruses comprise a diverse range of pathogenic viruses,
known to cause disease in both animals and human which often leads to high
fatality rates, many of which lack effective and approved therapeutics. This
report focuses on learning how a multifunctional protein within lipid enveloped
viruses, the matrix protein, interacts with the plasma membrane of cells to
enter and exit cells. Specifically, four viruses are investigated, Measles
virus and Nipah virus (within the <i>Paramyxoviridae</i> family) and Ebola
virus and Marburg virus (within the <i>Filoviridae</i> family). Through numerous
<i>in vitro </i>experiments, functional cellular assays, a myriad of microscopy
techniques, and experiments in high containment bio-safety level 4 settings,
this report identifies specific lipids at play during the viral assembly
process for each virus. Moreover, mechanistic insight is presented as to how
each matrix protein interacts with the plasma membrane to facilitate: membrane
association, viral matrix protein oligomerization and assembly, the
rearrangement of lipids within the plasma membrane, and viral production.
Lastly, numerous small molecule inhibitors targeting specific lipids, (e.g.
phosphatidylserine and phosphatidylinositol 4,5 bisphosphate) within the cell
were investigated for their efficacy in inhibiting matrix protein-dependent
viral like particle production and viral spread in cells. As a whole, these
projects lend credence to the significant role that lipids and the plasma
membrane play throughout lipid enveloped viral life cycles, and provide
compelling evidence for the merit of future drug-development research geared at
targeting the matrix protein-plasma membrane interaction.
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12250328 |
| Date | 07 May 2020 |
| Creators | Monica Leigh Husby (8801354) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Mechanisms_of_deadly_and_infectious_viruses_Learning_how_lipid_enveloped_viruses_assemble/12250328 |
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