Multistability in a Model for CTL Response to HTLV-I Infection and Its Implications to HAM/TSP Development and Prevention |
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Authors: | Horacio Gómez-Acevedo Michael Y Li Steven Jacobson |
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Institution: | 1.Department of Pediatrics,University of Arkansas for Medical Sciences,Little Rock,USA;2.Department of Mathematical and Statistical Sciences,University of Alberta,Edmonton,Canada;3.Viral Immunology Section,Neuroimmunology Branch NINDS/NIH,Bethesda,USA |
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Abstract: | Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is a retrovirus that has been identified as the causative agent of HTLV-I-associated
myelopathy/tropical spastic paraparesis (HAM/TSP) and other illnesses. HTLV-I infects primarily CD4+ T cells and the transmission occurs through direct cell-to-cell contact. HAM/TSP patients harbor higher proviral loads in
peripheral blood lymphocytes than asymptomatic carriers. Also, HAM/TSP patients exhibit a remarkably high number of circulating
HTLV-I-specific CD8+ cytotoxic T lymphocytes (CTLs) in the peripheral blood. While CTLs have a protective role by killing the infected cells and
lowering the proviral load, a high level of CTLs and their cytotoxicity are believed to be a main cause of the development
of HAM/TSP. A mathematical model for HTLV-I infection of CD4+ T cells that incorporates the CD8+ cytotoxic T-cell (CTL) response is investigated. Our mathematical analysis reveals that the system can stabilize at a carrier
steady-state with persistent viral infection but no CTL response, or at a HAM/TSP steady-state at which both the viral infection
and CTL response are persistent. We also establish two threshold parameters R
0 and R
1, the basic reproduction numbers for viral persistence and for CTL response, respectively. We show that the parameter R
1 can be used to distinguish asymptomatic carriers from HAM/TSP patients, and as an important control parameter for preventing
the development of HAM/TSP. |
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Keywords: | |
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