Emeritus ProfessorCharles Bangham, ScD FMedSci FRS

The human T cell leukaemia virus, HTLV-1
The human T-cell leukaemia virus, also known as human T-lymphotropic virus type 1 (HTLV-1) causes two distinct types of disease: an aggressive T-cell leukaemia/lymphoma and a number of chronic inflammatory conditions, notably HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In 90% of HTLV-1-infected individuals the virus persists indefinitely without causing disease. Neither the pathogenesis of these diseases nor the mechanism of persistent infection of HTLV-1 has been well understood.

We aim to answer three main questions. First, why does a minority of HTLV-I-infected people develop these fatal or disabling diseases, while the great majority remain asymptomatic carriers of the virus? Second, how does HTLV-I spread and persist in the host in the face of a strong cell-mediated immune response? Third, how does the virus regulate the balance between latency and reactivation in vivo?

To answer these questions we have studied host and virus genetic variation, lymphocyte phenotype and function, and the dynamics of HTLV-I replication and the cellular immune response. We have used techniques in molecular genetics, cellular immunology, cell biology, gene expression microarrays, proteomics and mathematical biology. Key contributions include:

discovery of tissue-resident antigen-specific T lymphocytes (J Exp Med 1998)
discovery of T-cell fratricide (Immunity 2000)
discovery of preferential infection of virus-specific T cells (Immunity 2000)
discovery of the virological synapse (Science 2003)
protective role of single HLA class 1 genes in viral infection at the population level (PNAS 1999)
importance of CD8+ T-cell quality in protection against persistent viruses (Science 1996)
regulation of HTLV-1 clonality and latency in vivo (Blood, PLoS Pathogens, PNAS etc, 2011-2016).
discovery that HTLV-1 alters the higher-order structure and transcription of host chromatin (PNAS 2016; eLife 2018).