TY  - THES
T1  - Analysis of HIV-host interaction on different scales
A1  - Bozek,Katarzyna
Y1  - 2012/01/20
N2  - The human immunodeficiency virus depends on molecular pathways of the host for efficient replication and spread. The intricate network of host-virus interactions shapes the virus'; evolution by driving the pathogen to evade immune recognition and constraining it to maintain its capacity to replicate. Study of the HIV-host interactions provides important insights into viral evolution, pathogenicity and potential treatment strategies. This thesis presents an analysis of HIV-host interactions on several scales, ranging from individual protein interactions to whole genomes. On the scale of individual interaction we analyze structural and physical determinants of the interaction between host TRIM5alpha and virus capsid — an interaction of potential therapeutic interest due to the capacity of TRIM5alpha to block retroviral infections. On the scale of viral population we present two studies of a highly variable region of the virus genome involved in the interaction with host cell coreceptors upon virus cell entry. The studies provide insights into the virus evolution and the physicochemical and structural properties related to its interaction with cellular coreceptors. On the scale of the single cell we develop models of HIV cell entry involving virus, host and environmental factors. The models represent a comprehensive picture of the virus phenotype and allow one to view the variability of virus phenotypes on 2D phenotype maps. On the genomic scale we perform a large-scale analysis of all HIV-host interactions. This study reveals insights into general patterns of the host-pathogen evolution and suggests candidate host proteins involved in interactions potentially important for the infection and interesting for further study on other scales. Interactions and processes crucial for the HIV infection reemerge across the scales pointing to the importance of integrative, multi-scale studies of host-pathogen biology.
KW  - HIV
KW  - Wirt
KW  - Interaktion
KW  - Replikation
KW  - statistische Analyse
KW  - Evolution
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2012/4529
ER  -