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Viral modulation of the immune system.

Douglas, Andrew Edward.

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Viral modulation of the immune system.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Viral modulation of the immune system./
作者:	Douglas, Andrew Edward.
面頁冊數:	112 p.
附註:	Advisers: Tracy M. Handel; James M. Berger.
Contained By:	Dissertation Abstracts International68-08B.
標題:	Biology, Virology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275396
ISBN:	9780549167389

Viral modulation of the immune system.
Douglas, Andrew Edward.

Viral modulation of the immune system. - 112 p.

Advisers: Tracy M. Handel; James M. Berger.

Thesis (Ph.D.)--University of California, Berkeley, 2007.

Viral infections trigger a strong response from the host's immune system. In order for the viruses to replicate and establish a persistent infection, they must express a variety of factors that interfere with and subvert the host response. This thesis focuses on structural work on two mechanisms of viral subversion; inhibition of apoptosis and interference with chemokine signaling.

ISBN: 9780549167389Subjects--Topical Terms:

1019068
Biology, Virology.

Viral modulation of the immune system.
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502 $a Thesis (Ph.D.)--University of California, Berkeley, 2007.
520 $a Viral infections trigger a strong response from the host's immune system. In order for the viruses to replicate and establish a persistent infection, they must express a variety of factors that interfere with and subvert the host response. This thesis focuses on structural work on two mechanisms of viral subversion; inhibition of apoptosis and interference with chemokine signaling.
520 $a Most viruses express multiple factors that inhibit both intrinsic and extrinsic apoptosis. This work focuses on determining the structure of two such anti-apoptotic factors from myxoma poxvirus, M11L and M-T2. M11L is known to inhibit intrinsic apoptosis through a mechanism similar to cellular Bcl-2. The structure of M11L was solved to 2.9A and was found to be a structural homolog of Bcl-2 despite a total lack of sequence homology. Using fluorescence polarization, the binding constant between M11L and Bak, one of its intracellular binding targets, was predicted to be 4.9 +/- 0.3muM. M-T2 is a secreted receptor that primarily binds and sequesters TNFalpha, a death ligand secreted by CD8+ cytotoxic T-lymphocytes to kill virally infected cells. Additionally, M-T2 can dimerize with cellular TNF receptors and inhibit their ability to signal. This thesis describes work to determine a suitable expression and purification system for MT-2 and its ligand rabbit TNFalpha. M-T2 was expressed at high levels using an insect cell/baculovirus expression system and purified using immobilized metal affinity chromatography.
520 $a Many viruses disrupt the recruitment of leukocytes to sites of infection by expressing soluble chemokine receptors. Many of these receptors are able to bind a broad range of chemokines with nanomolar affinities. Cowpox 35k and orfvirus CBP are two chemokine binding proteins that are studied in this thesis, towards the final goal of understanding how they are able to bind a broad range of ligands with high affinity. The proteins were expressed using HEK293s GnTI- cells to overcome previous difficulties with glycosylation. In addition, a novel expression system for producing chemokines for co-structures with the binding proteins is described. This new expression system will increase the range of chemokines that can be expressed and purified from E. coli.
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