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Rous sarcoma virus replication blocks in mammalian cells
Koslová, Anna ; Hejnar, Jiří (advisor) ; Ruml, Tomáš (referee) ; Weber, Jan (referee)
One of the important tasks of virology and immunology is to explore the species- and cell-barriers preventing virus horizontal transmission and reveal the ways how viruses overcome these barriers and "adapt" to different species. This work is based on a well- established retroviral model - avian Rous sarcoma virus (RSV) and studies virus replication blocks in mammalian cells at both pre- and post-integration level. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor mediates virus entry into cells. Although mammalian orthologues of specific chicken receptors do not support RSV entry, it was observed that some RSV strains are able to enter mammalian cells. Several RSV-transformed rodent cells lines were described and analysis of provirus H20- RSV in one these cells lines (hamster H-20 tumor cell line) showed multiple mutations including two crucial amino acid substitutions in different regions of Env. Substitutions D32G and L378S confer virus transmission to hamster, human and also chicken cells lacking the appropriate receptor. Altered conformation of H20-RSV Env is similar to a receptor-primed (activated) state of Env. This observation indicates that virus can circumvent the need of original cell receptor because of spontaneous Env activation caused by single...
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Molecular mechanisms of cellular nonpermissiveness against Rous sarcoma virus
Štafl, Kryštof ; Hejnar, Jiří (advisor) ; Hirsch, Ivan (referee)
Most viruses can infect only a reduced range of organisms and an effective replication is possible only in selected hosts. These hosts are called permissive for the virus. Molecular principles of a nonpermissiveness and viral mechanisms of overcoming replication obstacles are still not clearly elucidated. This thesis discusses the molecular causes of the cellular nonpermissiveness against a model retrovirus - Rous sarcoma virus. The research is conducted on duck cells which are semipermis- sive to the subgroup C of Rous sarcoma virus. The virus can enter those cells, but it is not able to produce enough infectious viral progeny. Two blocks of the viral replication cycle in the duck cells are described in the thesis. The first one is the probably not optimal cellular receptor recognition. The second one is in the late phase of the replication cycle when the viral proteins are synthesized. The amount of the envelope glyco- protein coding mRNA is reduced due to the altered splicing ratios, and the virions produced from the duck cells are less infectious. This block is recessive and can be partially omitted by cell fusions with permissive chicken cells; therefore, the block is not caused by specific restriction fac- tors in sensu stricto. Additionally, the influence of mutations in duck adapted Rous...
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Host factors involved in Rous Sarcoma Virus replication
Štafl, Kryštof ; Svoboda, Jan (advisor) ; Horníková, Lenka (referee)
Rous sarcoma virus (RSV) takes a place of honor among retroviruses. Research of RSV allows us to uncover the secret of the origin and evolution of life, the mechanisms of tumorigenesis and the interaction between viruses and their hosts. Viruses are not able to replicate themselves without host cells. They exploit a number of cellular pathways and factors and they can reprogram the cells to produce great amounts of viral progeny. They exert pressure on their host that leads to developement of new types of cellular proteins, which then results in resistance of the cells. This thesis focuses on the host factors involved in the RSV replication cycle. It summarizes the current knowledge about the replication cycle of retroviruses and the host factors that are necessary for productive infection: cellular receptors, endocytic and secretory pathways, nuclear transport, proteosynthesis, replication of proviruses and its stimulation. The restriction mechanisms of cells are also taken into account. The current knowledge about RSV is compared with facts on mammalian retroviruses and gaps in research are highlighted. The influence of the host cell factor absence, host specificity and cellular permissiveness are correlated and discussed.
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