Nucleocytoplasmic large DNA viruses (NCLDVs) have genome sizes that range from around 100 kilobases (kb) to up to 2.5 megabases, and virion sizes that can reach up to 1.5 μm. Their large size in both of these contexts is atypical and defies the traditional view that viruses are streamlined, "filterable infectious agents". NCLDVs include many diverse groups, including Poxviruses, Asfarviruses, Iridoviruses, Mimiviruses, and Marseilleviruses. Poxviruses are perhaps the most well-studied; these viruses have 135-360 kbp genomes with about half of the genes encoding essential replication genes and the other half encoding genes related to host-virus interactions. Many of the genes involved in host-virus interactions are involved in immunomodulatory processes and have homology to proteins encoded by the host. These viral genes, often referred to as "mimics", are therefore believed to be the result of host-to-virus gene transfer. In this study I sought to examine if common poxvirus immunomodulatory genes were found in other NCLDV lineages, and if so, to analyze the evolutionary history of these genes. I identified 5 protein families of immunomodulatory genes that were found in both poxviruses and other NCLDV lineages, and I used phylogenetic tools to compare viral immunomodulatory genes of NCLDVs to their eukaryotic orthologs to evaluate the number of times different NCLDV lineages have acquired these genes. Our phylogenetic analyses showed that several viral immunomodulatory genes were acquired multiple times by different NCLDV lineages, while others appear to have been transferred between viral groups. Interestingly, some NCLDV genes clustered together with homologs from the unrelated Herpesviridae family, suggesting that inter-viral gene exchange can traverse vast evolutionary distances. The vast diversity of hosts infected by different NCLDV lineages suggests that these immunomodulatory genes play key roles that are useful to viruses in a variety of contexts. This research provides insight into how giant viruses acquire host genes, which contribute to their large genome size, and how those genes evolved to subvert antiviral defenses. / Master of Science / Giant viruses are a relatively recent discovery, from the beginning of this century. Nucleocytoplasmic large DNA viruses (NCLDVs) are a classification of multiple giant virus families. These viruses have large genomes from around 100 kilobases to 2.5 megabases of DNA. For reference, the genome size of the flu virus is approximately 13 kilobases. Most viruses cannot be seen by the human eye, even with microscopes, but giant viruses can get as big as bacteria, which can be seen with microscopes. It is unknown how or why these viruses get so large. One explanation is that they steal genes from their host and those genes evolve to work against the host. In this thesis, I explored some of the genes that these viruses have picked up. I curated a set of 49 previously characterized viral genes to analyze in this context. These genes have to do with modulating the host immune system and are known as "immunomodulatory genes". Viral immunomodulatory genes are often mimics of the host genes which function to help the immune system. However, a virus evolves faster than a host and the virus mimic gene can evolve to work against the immune system. This change can be visualized using phylogenetic tools; the viral genes will be more similar to each other than to the host genes and cluster separately on a phylogenetic tree. About half of the genes of Poxviruses, a giant virus family that has viruses that infect humans, are related to virus-host interactions, and include viral mimic genes. Poxviruses have been far better studied than other NCLDV families because of their public health importance. Variola virus, the virus that causes smallpox, is a poxvirus. Other NCLDV infect animals, algae, and amoeba. Though their hosts are different, their genomes have similar features. I set out to discover whether some of these previously characterized viral immunomodulatory genes that exist in poxviruses also exist in other NCLDV families. I utilized phylogenetic tools and a database of giant virus sequences to figure out which genes are being picked up by which family of NCLDV. I also sought to determine whether the individual NCLDV families have their own acquired immunomodulatory gene or have a gene very similar to all other families, suggesting an ancient acquisition. If the gene is very similar, it suggests that an ancestor of the NCLDV acquired the gene and it has stuck around as the group diverged into families. It is also interesting if different families stole the same type of gene multiple times because that indicates the importance of that gene in subverting the antiviral immune system for viral replication. This work provides insight into how giant viruses acquire host genes, which contribute to their large genome size, and how they evolved those genes to subvert antiviral defenses.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/110124 |
| Date | 20 May 2022 |
| Creators | Perez, Claudia Elizabeth |
| Contributors | Biological Sciences, Aylward, Frank O., Belden, Lisa Kay, Duggal, Nisha K. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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