Nature (2016)
Cartoon illustration of the drug concentration-dependent spatial model. (Nature 2016) See below.

A team of international researchers including scientists from Oxford University has found that HIV is still replicating in lymphoid tissue even when it is undetectable in the blood of patients on antiretroviral drugs.

The findings provide a critical new perspective on how HIV persists in the body despite potent antiretroviral therapy.

The study, led by Northwestern University, USA and University of Oxford, is published in the journal Nature.

“Deep sequencing is able to detect mutations in the virus that are present at very very low numbers,” says Helen Fryer. “We wanted to see if we could find mutational changes that are consistent with viruses going through cycles of replication. We know as HIV replicates, it makes mistakes pretty much every time it infects a new cell.”

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Promoting discussion between HIV Specialists

Three members of the Institute for Emerging Infections have participated in the 23rd International HIV Dynamics and Evolution meeting. The three-day meeting was held in the Marine Biological Laboratory, set in Woods Hole, a beautiful coastal town in the southwest corner of Cape Cod.

This annual event aims to promote discussion on statistical, mathematical and computational approaches to analysing the dynamics and evolution of HIV-1. Themes that were covered in this years’ conference included viral reservoirs, drug resistance, within-host dynamics and epidemiology.

Professor Angela McLean, who is a member of the organizing committee, attended the meeting alongside Hannah Roberts and Dr Helen Fryer. Day one saw Hannah Roberts present a poster investigating why starting antiretroviral therapy in acutely infected patients leads to prolonged control after treatment interruption. On the final day of the meeting, Helen Fryer presented a new idea for HIV-clearance. She described how this idea was borne from her modelling work to characterise how persistent replication in drug sanctuaries could be topping up the HIV-1 reservoir in patients taking antiretroviral therapy. Both women received positive and constructive feedback on their work.

As well as being highly enjoyable and thought provoking, the event was a great opportunity to catch up with collaborators and past colleagues.

Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency

While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences.

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Hannah Roberts recently spent 3 months on a Research Councils UK policy internship, based at the National Assembly for Wales' Research Service. She was able to get involved in all aspects of the work of the Research Service's Health and Social Care team, which includes responding to regular enquiries from Assembly Members and writing proactive briefing papers on areas that are likely to be of interest to Members and relevant to the work of the Assembly. She very much enjoyed the experience and learnt a lot about writing in a clear, impartial and engaging manner, and about Welsh politics!

Daniel

Daniel Wilson of the Oxford Martin School Programme on Curing Chronic Viral Infections has been awarded a prestigious Henry Dale Fellowship.

His project entitled "Statistical methods for whole genome phenotype mapping in bacterial populations" will address the question of how to detect genes or mutations in bacteria that increase the chances of causing severe infection.

The award consists of 5 years funding for Daniel and additional funds for a research assistant and associated lab costs.

Helen Fryer and Angela McLean from of the Institute for Emerging Infections have published important new findings on the risk from prions, the infectious agent responsible for ‘mad cow disease’ and variant Creutzfeldt-Jakob disease (vCJD). Based on ideas from toxicology and radiology, it is often assumed that exposure to harmful agents, including prions, is completely safe at low enough doses. The study, published in the journal PLoS One, is the first to investigate the existence of a threshold dose of prions, below which the probability of infection is zero. Using mathematical tools to analyse data from over 4000 prion experiments, the pair have revealed that there is no evidence for the existence of such a threshold dose. The implications are profound for managing risks such as the potential transfer of vCJD via surgical instruments. The findings suggest that although very small quantities of prions may pose a very small risk of infection, that risk does not disappear as the dose becomes smaller.

Dr Jenny Smith, former Oxford Martin School Fellow, has been awarded an Oxford DPhil for her work on the viral diversity and dynamics of hepatitis C. Jenny continues to work as a Mathematical Biologist at Imperial College London, and we wish her every success for the future.

Jenny's thesis combined observational and modelling work to explore the causes and consequences of within-host competition between different strains of Hepatitis C Virus. In her first paper http://jid.oxfordjournals.org/content/202/12/1770.full she published these beautiful descriptions of the dynamics of HCV quasispecies clades within subjects through acute infection.

Professor Angela McLean, Co-Director of the Institute for Emerging Infections, has joined the Royal Society’s Scientific Aspects of International Security (SAIS) Committee

SAIS was established in 1988 and considers a range of security issues, including: arms control and non-proliferation; governance of ‘dual-use’ scientific research; security impacts of developing science and technology; and counter-terrorism.

Its principal role is to advise the Royal Society’s Science Policy Centre (SPC), and the SPC Advisory Group that oversees the Centre, on international security issues.  The expertise on the committee covers a wide range of disciplines and the current membership includes Royal Society Fellows and other scientists, as well as science and security policy experts.

The mission of the Institute for Emerging Infections is to understand the underlying processes that drive the emergence and spread of novel human infectious diseases. A multi-disciplinary team of biologists, mathematicians and clinicians are studying recently emerged infections and using the knowledge thus gained to anticipate challenges that will be posed by novel emergent infections in the 21st century.