Role of nuclear paraspeckles in regulating HSV-1 infection in neurons

About This Grant

7. PROJECT SUMMARY/ABSTRACT Nuclear speckles and paraspeckles are dynamic subnuclear ribonucleoprotein structures that play critical roles in the regulation of gene expression and RNA processing. Increasing evidence suggests that these structures regulate HSV-1 replication in HeLa cells and mouse embryonic fibroblasts (MEFs). However, the mechanisms by which components of nuclear speckles and paraspeckles regulate HSV-1 gene expression in human neurons, as well as their potential role in establishing HSV-1 latency, have yet to be explored. This proposal aims to investigate aspects of the roles played by nuclear speckles and paraspeckles in modulating HSV-1 gene expression in human neurons, as well as to explore how these structures contribute to the establishment and maintenance of HSV-1 latency. In Aim 1, we will investigate whether silencing of paraspeckle-associated genes (NEAT1, PSPC1, NONO, and SFPQ) prevents the silencing of HSV-1 lytic genes and, as a consequence, inhibition of viral replication and suppression of productive infection in our iPSC-derived neuronal model of HSV-1 latency. In Aim 2, we will investigate the involvement of nuclear speckles and paraspeckles in epigenetic modulations of HSV-1 chromatin underlying the establishment of HSV-1 latency. Results from this study will provide essential insights into the role of paraspeckles in regulating HSV-1 infection in human neurons, paving the way for future research and potential clinical applications.