DocumentCode :
3496061
Title :
Computational analysis and modelling of intra-host adaptation of hepatitis C virus: The role of immune cross-reactivity of HCV quasispecies
Author :
Skums, Pavel ; Campo, David S. ; Dimitrova, Zoya ; Bunimovich, Leonid ; Khudyakov, Yury
Author_Institution :
Centers of Disease Control & Prevention, Atlanta, GA, USA
fYear :
2013
fDate :
12-14 June 2013
Firstpage :
1
Lastpage :
1
Abstract :
Hepatitis C virus (HCV) is a major cause of liver disease worldwide. Understanding the mechanisms responsible for the establishment of chronic HCV infection is critical to the development of efficient therapeutics and vaccines. The mechanism of intra-host HCV evolution assumed by most models is based on immune escape via random mutations. However, continuous immune escape does not explain our observation of a consistent increase in negative selection during chronic infection, which suggests extensive intra-host HCV adaptation. Using a model of cross-immunoreactivity, we show that the level of HCV intra-host adaptation correlates with the rate of cross-immunoreactivity among HCV quasispecies. We present a mathematical model describing the immunological interaction among quasispecies that involves, in addition to neutralization, a non-neutralizing cross-immunoreactivity. The model describes how HCV variants escape immune responses and persist, owing to their capability to stimulate non-neutralizing immune responses developed earlier against preceding variants without eliciting specific responses against the variant itself.
Keywords :
diseases; liver; mathematical analysis; microorganisms; random processes; HCV quasispecies; chronic HCV infection establishment; computational analysis; computational modelling; hepatitis C virus; immune cross-reactivity; immune escape; immunological interaction; intrahost adaptation; liver disease; mathematical model; nonneutralizing cross-immunoreactivity; nonneutralizing immune response simulation; random mutations; therapeutics; vaccines; Adaptation models; Analytical models; Electronic mail; Immune system; Mathematical model; Sociology; Statistics;
fLanguage :
English
Publisher :
ieee
Conference_Titel :
Computational Advances in Bio and Medical Sciences (ICCABS), 2013 IEEE 3rd International Conference on
Conference_Location :
New Orleans, LA
Type :
conf
DOI :
10.1109/ICCABS.2013.6629220
Filename :
6629220
Link To Document :
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