Viral infection severity often varies with host factors such as age and sex. The pathogenesis
of infections caused by a broad range of viruses, from neurotropic viruses like Rabies and Zika
to respiratory viruses such as Influenza and SARS-CoV-2, differ between the sexes and across
the lifespan. Typically, older males are more susceptible to severe acute outcomes, while females are more vulnerable to the post-acute sequelae of infections. All of these complications can include neuroinflammation, stroke, cognitive dysfunction, and delirium. While these symptoms can be secondary to infection, recent studies suggest that even peripheral infections can lead to neuropathological changes in the brain. However, few studies have characterized the expression of viral receptors in the human brain or examined age- or sex-related differences in such expression. In this study, we used a publicly accessible transcriptomic database to assess the impact of age and sex on the expression of 67 viral host factor genes, associated with ten virus families. Analyzing data from 15 brain areas (n=33, F=14, M=19, age:4 mo-80 yrs), we determined the lifespan trajectory for each gene in each area via LOESS regressions. We used unsupervised hierarchical clustering to determine if a brain-wide pattern or virus family pattern can be detected. Using Dense-tSNE, a dimension-reduction and visualization technique, we discovered four distinct developmental trajectories, clustering the areas into two mixed-sex subcortical clusters and one each of male and female cortical clusters. Applying Differential Expression Sliding Window Analysis (DeSWAN), we identified the genes driving these age- and sex-related differences. Many sex differences were noted in childhood, potentially impacting the brain's susceptibility to viral infections and underscoring a broader dimorphic organization of male and female brains. These insights contribute to our understanding of sex-specific responses to viral infections, offering the potential for more personalized treatment strategies. / Thesis / Master of Science (MSc) / Viral infections, like Influenza and SARS-CoV-2, vary in severity based on a person's age
and sex. Generally, older men suffer severe immediate symptoms such as stroke and seizures, while women endure long-term effects, including brain inflammation and cognitive issues. Recent research suggests even non-brain-related infections can lead to changes within the brain. Yet, our understanding of how our brains' viral receptors - key to infection - change with age and between sexes is limited. We used a public database to explore these changes, studying receptor-related genes in different brain areas across various ages and sexes. Our analysis revealed unique patterns of gene expression, grouping the brain into different regions based on development and sex. We noticed many differences between men and women during childhood, potentially influencing how their brains respond to viruses. This research aids our understanding of why viral infections impact individuals differently based on age and sex, offering insights that could help develop personalized treatments.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28750 |
| Date | January 2023 |
| Creators | Halabian, Negeen |
| Contributors | Murphy, Kathryn M., Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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