HTLV-I infection: A dynamic struggle between viral persistence and host immunity

Aaron G Lim, Philip K Maini

Research output: Contribution to journalArticle (Academic Journal)peer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)92-108
Number of pages17
JournalJournal of Theoretical Biology
Volume352
DOIs
Publication statusPublished - 7 Jul 2014

Bibliographical note

Copyright © 2014 Elsevier Ltd. All rights reserved.

Keywords

  • HTLV-I Infections
  • Host-Pathogen Interactions
  • Human T-lymphotropic virus 1
  • Humans
  • Viral Load
  • Virus Activation

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