Understanding the impact of hypoxia on HIV replication and latency

Project Overview

Background:  

Hypoxia Inducible Factors (HIFs) are ancient transcription factors regulated by oxygen-dependent and independent stress signals that control a wide range of genes involved in energy metabolism and inflammation. Mounting evidence shows a role for HIFs in a number of diseases including cancer and inflammatory conditions, where pharmacological approaches to modulate HIF activity offer promising therapeutic avenues. However, the role of HIFs in chronic viral infection is poorly understood.

Human immunodeficiency virus type 1 (HIV-1) is a globally important infection and current therapies control viral replication but fail to eradicate long-lived cellular HIV reservoirs. Oxygen tensions differ across tissues and HIV infected T cells within lymphoid tissues will experience a hypoxic environment (1% O2) compared to those trafficking in the periphery (13% O2 in arterial blood). Recent studies in our laboratory show that low oxygen inhibits HIV-1 replication and reactivation from latent reservoirs via a HIF dependent process.

The successful candidate will extend these studies by investigating the molecular mechanisms underlying these observations. In particular, we will (i) identify the molecular mechanisms by which HIFs restrict HIV replication, (ii) analyse how these host-virus interactions are shaped by the tissue microenvironment. The project has basic and translational research components. Taken together, this exciting project builds on strong preliminary results and will increase our understanding of host immune responses to HIV. 

Training Opportunities

The successful candidate will be based in the NMD Research Building that provides state-of-the-art facilities and an opportunity for training in a broad range of different techniques, including cell culture, molecular biology, immunology and virology. This project will additionally benefit from close collaboration with many scientists. The successful candidate will be co-supervised by Jane McKeating and Seph Borrow and additional day-to-day supervision will be provided by experienced members of both labs.

Theme

Immunology & Infectious Disease

Admissions

Project reference number: 952

Funding and admissions information

Supervisors

Name Department Institution Country Email
Professor Jane McKeating NDM Research Building Oxford University, NDM Research Building GBR jane.mckeating@ndm.ox.ac.uk
Professor Persephone Borrow NDM Research Building Oxford University, NDM Research Building GBR persephone.borrow@ndm.ox.ac.uk

There are no publications listed for this DPhil project.