Exploring the Role of SAMHD1: From Viral Restriction to Cancer and Drug Development

TOPICAL COLLECTIONS

Guest Editors

Chloe Tsai

The Francis Crick Institute

Dr. Chloe Tsai is a Postdoctoral Training Fellow in the Retroviral Replication Laboratory at the Francis Crick Institute. Her research interests focus on HIV-1 immunopathogenesis and viral restriction factor SAMHD1. Her early work at Imperial College London assessed the prevention of HIV-1-induced immune activation of plasmacytoid dendritic cells (pDCs) by using chloroquine-derivatives. While pursuing her PhD at the University of Oxford, she investigated virus controllers with low immune activation and their landscape of CD8+ T cell epitopes across HIV-1 subtype B, C, and CRF07_BC from South African, Indian, and Taiwanese cohorts. Following her passion for HIV-1 immunology and host-virus interaction, Dr Tsai’s post-doctoral research explores the role of viral restriction factor SAMHD1 in activated monocytes and T cells, as well as the impact of viral accessory protein Vpr on the early spread of immune cells populations.

Liz Morris

The Francis Crick Institute, London, United Kingdom

Dr Liz Morris is a Postdoctoral Training Fellow at the Francis Crick Institute in London. Her recent work focuses on the HIV-1 restriction factor SAMHD1, using structural biology and enzymological methods to determine the chemical detail of its dNTP hydrolase catalytic mechanism. Prior to the Crick, Dr Morris pursued a postdoctoral project at the University of Edinburgh, after completing her undergraduate and master's degrees in Natural Sciences (Chemistry) at the University of Cambridge and her PhD (Chemistry) at the University of Nottingham.

Collection Overview

SAMHD1 is a fundamental regulator of cellular dNTPs that catalyses their hydrolysis into component 2’-deoxynucleoside and inorganic triphosphate. The dNTP hydrolase activity of SAMHD1 restricts the replication of certain retroviruses, such as human immunodeficiency virus (HIV), as well as some DNA viruses and endogenous retroelements. SAMHD1 is also an important effector of innate immunity, and SAMHD1 mutations are found in patients with autoimmune disease Aicardi-Goutières Syndrome, early onset stroke, as well as chronic leukaemia, and other cancers. SAMHD1 expression in acute myelogenous leukaemia patients is associated with efficacy reduction of some nucleoside-analogue anti-cancer drugs, as a result of SAMHD1 hydrolysis of their triphosphorylated forms. More recently, SAMHD1 has been reported to have a hydrolase-independent function in genome maintenance pathways, facilitating homologous recombination and functioning in DNA repair to suppress the release of single-stranded DNA fragments from stalled replication forks into the cytosol. To study the diverse cellular and anti-viral functions of SAMHD1, a wide range of methodologies have been employed to date. In this SAMHD1-focused Methods Collection, we are gathering research methods across this broad field, including, but not limited to; protein structure determination, enzymological assays, cellular nucleotide measurements, anti-cancer drug efficacy studies, viral restriction assays, and DNA repair experiments, as well as others that can further our understanding of SAMHD1’s cellular functions.