Deciphering cellular and viral determinants of lytic HSV-1 infection, latency and reactivation

Introduction

Herpes simplex virus 1 (HSV-1) is an important human pathogen that infects the majority of the world's population and inflicts a substantial burden of disease. Over the past 10 years, systems biology approaches, to which my lab has provided seminal contributions, have substantially broadened our understanding of the complex interaction of this common pathogen with its human host.

Knowledge Gaps

However, the underlying molecular mechanisms remain poorly understood, and their importance for virus latency and reactivation remains elusive. Furthermore, currently available technology lacks the temporospatial resolution to decipher the cellular and viral determinants that govern the virus life cycle.

Project Goals

The main goal of DecipherHSV is to close these knowledge and technology gaps and decipher novel mechanisms and their functional interplay by which HSV-1 manipulates its host cells throughout the virus life cycle.

Objectives

Accordingly, the three primary objectives of DecipherHSV are to:

1. Decipher the full complement of viral elements that govern productive infection.
2. Decipher how and why HSV-1 manipulates pervasive transcription within the host and viral genome.
3. Decipher the cellular and viral determinants of HSV-1 latency and reactivation.

Methodology

Alongside, I will develop new computational approaches and integrative analysis tools, and employ artificial intelligence to exploit the wealth of information that is provided by the novel single-cell RNA sequencing approaches, which I will pioneer (Heterogeneity-seq and Perturb-scSLAM-seq).

Expected Outcomes

Thereby, I will deliver new leads for novel therapeutic approaches targeting HSV-1 latency and reactivation. This will provide a paradigm for the study of other herpesviruses and their complex host-pathogen interactions.