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Underwhelming the immune response: Effect of slow virus growth on CD8+-T-lymphocyte responses

Bocharov, Gennady
; 
Burkhard, Ludewig
; 
Bertoletti, Antonio
; 
Klenerman, Paul
; 
Junt, Tobias
; 
Krebs, Philippe
; 
Luzyanina, Tatyana
; 
Fraser, Cristophe
; 
Anderson, Roy M.
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Affiliation
University of London/Institute of Numerical Mathematics, Russian Academy of Sciences ; University of Zurich ; University College London ; Oxford University ; University of Zurich ; University of Zurich ; Leuven University ; University of London ; University of London
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Publication Date
2004-02-12
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Mathematics
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Abstract
The speed of virus replication has typically been seen as an advantage for a virus in overcoming the ability of the immune system to control its population growth. Under some circumstances, the converse may also be true: more slowly replicating viruses may evoke weaker cellular immune responses and therefore enhance their likelihood of persistence. Using the model of lymphocytic choriomeningitis virus (LCMV) infection in mice, we provide evidence that slowly replicating strains induce weaker cytotoxic-T-lymphocyte (CTL) responses than a more rapidly replicating strain. Conceptually, we show a "bell-shaped" relationship between the LCMV growth rate and the peak CTL response. Quantitative analysis of human hepatitis C virus infections suggests that a reduction in virus growth rate between patients during the incubation period is associated with a spectrum of disease outcomes, from fulminant hepatitis at the highest rate of viral replication through acute resolving to chronic persistence at the lowest rate. A mathematical model for virus-CTL population dynamics (analogous to predator [CTL]-prey [virus] interactions) is applied in the clinical data-driven analysis of acute hepatitis B virus infection. The speed of viral replication, through its stimulus of host CTL responses, represents an important factor influencing the pathogenesis and duration of virus persistence within the human host. Viruses with lower growth rates may persist in the host because they "sneak through" immune surveillance.
Citation
Journal of Virology, 2004, 78(5), pp. 2247-2254
Publisher
American Society for Microbiology
Journal
Journal of Virology
Research Unit
URI
http://hdl.handle.net/10034/97005
DOI
10.1128/JVI.78.5.2247-2254.2004
PubMed ID
PubMed Central ID
Type
Article
Language
en
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ISSN
0022-538X
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This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.
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http://jvi.asm.org