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

Hdl Handle:
http://hdl.handle.net/10034/97005
Title:
Underwhelming the immune response: Effect of slow virus growth on CD8+-T-lymphocyte responses
Authors:
Bocharov, Gennady; Burkhard, Ludewig; Bertoletti, Antonio; Klenerman, Paul; Junt, Tobias; Krebs, Philippe; Luzyanina, Tatyana; Fraser, Cristophe; Anderson, Roy M.
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.
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
Citation:
Journal of Virology, 2004, 78(5), pp. 2247-2254
Publisher:
American Society for Microbiology
Journal:
Journal of Virology
Publication Date:
Mar-2004
URI:
http://hdl.handle.net/10034/97005
DOI:
10.1128/JVI.78.5.2247-2254.2004
Additional Links:
http://jvi.asm.org
Type:
Article
Language:
en
Description:
This article is not available through ChesterRep.
ISSN:
0022-538X
Sponsors:
This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.
Appears in Collections:
Mathematics

Full metadata record

DC FieldValue Language
dc.contributor.authorBocharov, Gennadyen
dc.contributor.authorBurkhard, Ludewigen
dc.contributor.authorBertoletti, Antonioen
dc.contributor.authorKlenerman, Paulen
dc.contributor.authorJunt, Tobiasen
dc.contributor.authorKrebs, Philippeen
dc.contributor.authorLuzyanina, Tatyanaen
dc.contributor.authorFraser, Cristopheen
dc.contributor.authorAnderson, Roy M.en
dc.date.accessioned2010-04-21T11:54:20Zen
dc.date.available2010-04-21T11:54:20Zen
dc.date.issued2004-03en
dc.identifier.citationJournal of Virology, 2004, 78(5), pp. 2247-2254en
dc.identifier.issn0022-538Xen
dc.identifier.doi10.1128/JVI.78.5.2247-2254.2004en
dc.identifier.urihttp://hdl.handle.net/10034/97005en
dc.descriptionThis article is not available through ChesterRep.en
dc.description.abstractThe 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.en
dc.description.sponsorshipThis article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.relation.urlhttp://jvi.asm.orgen
dc.subjectvirus replicationen
dc.subjectimmune systemen
dc.titleUnderwhelming the immune response: Effect of slow virus growth on CD8+-T-lymphocyte responsesen
dc.typeArticleen
dc.contributor.departmentUniversity 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 Londonen
dc.identifier.journalJournal of Virologyen
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