Natasha Preston
Academic and research departments
Section of Virology, Department of Microbial Sciences, School of Biosciences.About
My research project
Innate immune responses to HSV1 in human skin.This project uses a two-pronged approach to investigate the innate immune response to HSV-1; investigating the role of the HSV-1 accessory protein UL13 in counteracting antiviral responses, and characterising the innate immune response to HSV-1 in human keratinocyte models.
Supervisors
This project uses a two-pronged approach to investigate the innate immune response to HSV-1; investigating the role of the HSV-1 accessory protein UL13 in counteracting antiviral responses, and characterising the innate immune response to HSV-1 in human keratinocyte models.
My qualifications
Affiliations and memberships
Previous Roles
2021-2022: Research Associate - Purification and Conjugation, Abcam (Cambridge)
2019-2020: Student Flavour Research Analyst, Synergy Flavours (High Wycombe)
Publications
Many viruses downregulate their cognate receptors, facilitating virus replication and pathogenesis via processes that are not yet fully understood. In the case of herpes simplex virus 1 (HSV1), the receptor binding protein glycoprotein D (gD) has been implicated in downregulation of its receptor nectin1, but current understanding of the process is limited. Some studies suggest that gD on the incoming virion is sufficient to achieve nectin1 downregulation, but the virus-encoded E3 ubiquitin ligase ICP0 has also been implicated. Here we have used the physiologically relevant nTERT human keratinocyte cell type - which we have previously shown to express readily detectable levels of endogenous nectin1 - to conduct a detailed investigation of nectin1 expression during HSV1 infection. In these cells, nectin1, but not nectin2 or the transferrin receptor, disappeared from the cell surface in a process that required virus protein synthesis rather than incoming virus, but did not involve virus-induced host shutoff. Furthermore, gD was not only required but was sufficient for nectin1 depletion, indicating that no other virus proteins are essential. NK cells were shown to be activated in the presence of keratinocytes, a process that was greatly inhibited in cells infected with wild-type virus. However, degranulation of NK cells was also inhibited in ΔgD-infected cells, indicating that blocking of NK cell activation was independent of gD downregulation of nectin1. By contrast, a superinfection time-course revealed that the ability of HSV1 infection to block subsequent infection of a GFP-expressing HSV1 was dependent on gD and occurred in line with the timing of nectin1 downregulation. Thus, the role of gD-dependent nectin1 impairment during HSV infection is important for virus infection, but not immune evasion, which is achieved by other mechanisms.