Infection and Immunity Group

Professor Andrew Lloyd

The Infection & Immunity Group includes two major research themes: firstly studies of the determinants of severity and course of the acute sickness response associated with infection, and secondly studies of the immunopathogenesis of hepatitis C (HCV) infection. The first research theme includes studies of post-infective fatigue syndrome. The research is based on a unique prospective cohort study – the Dubbo Infection Outcomes Study (DIOS), which is following individuals from the time of onset of documented infection with Epstein-Barr virus (EBV), Ross River virus (RRV) or Q fever infection. The co-investigators in this project include Professor Denis Wakefield, in addition to Dr Ute Vollmer-Conna from the School of Psychiatry. During 2008, the DIOS project was supported by funding from the Mason Foundation, including grants for studies of: gene expression in post-infective fatigue syndrome in collaboration with Dr Sally Galbraith from the School of Mathematics and Statistics at UNSW; and studies of autonomic nervous system functioning in post-infective syndrome.
A key observation in the DIOS cohort was that the severity of the acute infective illness was a very strong predictor of the likelihood of protracted illness after the acute infection (i.e. post-infective fatigue syndrome), whereas demographic, microbiological, and psychological characteristics were not predictive. Given this observation, and a previous finding from the Group that pro-inflammatory cytokine production correlated with severity of symptoms in the acute illness, during 2008 the Group published data examining the impact of functional polymorphisms in cytokine genes with critical roles in the early immune response (tumor necrosis factor–a, interleukin-6, interleukin-10, and interferon-g) on the severity and duration of illness following acute infection. The interferon-g +874T/A and the interleukin-10 -592C/A polymorphisms were associated with illness severity and duration as well as cytokine protein levels. These cytokine genotypes acted in synergy to potentiate their in?uence on disease outcomes. Current studies are examining functional polymorphisms in neurobehavioural genes also likely to have relevance to manifestations of the acute sickness response to infection.

The HCV studies are conducted in collaboration with virologists, A/Professor Peter White, School of Biotechnology and Biomolecular Sciences and Professor Bill Rawlinson at Prince of Wales Hospital. Liver disease associated with the convergent epidemics of obesity and HCV are the focus of studies led by Dr Zekry in the Group. In particular, the effects of fat-derived mediators - adipokines on the characteristics of the antiviral immune response against HCV are being investigated. The major focus during 2008 has been investigation of the cytokine and chemokine expression patterns in liver tissue of individuals who are either lean or obese and have chronic HCV infection, in comparison to individuals without HCV infection who have non-alcoholic steatohepatitis (NASH) or normal liver histology. In addition, the pattern of interferon-stimulated gene (ISG) expression in individuals receiving antiviral therapy for chronic HCV is being studied.
The Hepatitis C Incidence and Transmission Study (HITS) cohort is a well-established prospective study of NSW prisoners funded by a Strategic Priorities Grant from UNSW (2007-2009) for the UNSW HCV Vaccine Initiative. In this Initiative the prison cohort (HITS-p) has provided the framework for the development of a comparable community-based cohort (HITS-c) under the leadership of A/Professor Lisa Maher and A/Professor Greg Dore from the National Centre in HIV Epidemiology and Clinical Research (NCHECR). The clinical, virological, and immunological features of primary hepatitis C infections are being studied in incident cases arising from these cohorts (HITS-i). In addition, studies are underway examining aspects of potentially protective immunity against HCV discovered by the Group in individuals highly exposed, but uninfected, with the virus. This Initiative is conducted in collaboration with investigators from NCHECR, the National Centre in HIV Social Research (NCHSR) and the National Drug and Alcohol Research Centre (NDARC).