title: HTLV-I infection: a dynamic struggle between viral persistence and host immunity.
abstract: Human T-lymphotropic virus type I (HTLV-I) causes chronic infection for which there is no cure or neutralising vaccine. HTLV-I has been clinically linked to the development of adult T-cell leukaemia/lymphoma (ATL), an aggressive blood cancer, and HAM/TSP, a progressive neurological and inflammatory disease. Infected individuals typically mount a large, persistently activated CD8(+) cytotoxic T-lymphocyte (CTL) response against HTLV-I-infected cells, but ultimately fail to effectively eliminate the virus. Moreover, the identification of determinants to disease manifestation has thus far been elusive. A key issue in current HTLV-I research is to better understand the dynamic interaction between persistent infection by HTLV-I and virus-specific host immunity. Recent experimental hypotheses for the persistence of HTLV-I in vivo have led to the development of mathematical models illuminating the balance between proviral latency and activation in the target cell population. We investigate the role of a constantly changing anti-viral immune environment acting in response to the effects of infected T-cell activation and subsequent viral expression. The resulting model is a four-dimensional, non-linear system of ordinary differential equations that describes the dynamic interactions among viral expression, infected target cell activation, and the HTLV-I-specific CTL response. The global dynamics of the model is established through the construction of appropriate Lyapunov functions. Examining the particular roles of viral expression and host immunity during the chronic phase of HTLV-I infection offers important insights regarding the evolution of viral persistence and proposes a hypothesis for pathogenesis.
authors.affiliation: Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK. Electronic address: aaron.lim@maths.ox.ac.uk.
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Lim
authors.affiliation: Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK. Electronic address: maini@maths.ox.ac.uk.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Maini
mesh_terms: D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D019562:Viral Load; D014775:Virus Activation
keywords: CTL response; Global stability; Infected target cell latency; Mathematical modelling; Proviral activation