Item Details

title

Vesicular stomatitis virus induced apoptosis occurs by a mechanism involving the activation of pro-apoptotic Bcl-2 proteins Bak and Bid and the inactivation of anti-apoptotic Bcl-2 proteins Bcl-XL and Mcl-1

author

Pearce, Alicia

abstract

In the first chapter of my thesis I address the question of what role Bcl-2 family proteins play in apoptosis induced by vesicular stomatitis virus (VSV) with wild-type (wt) M protein (rWT virus). My results demonstrate that of the two major proapoptotic multidomain proteins Bak and Bax, Bak is more important for the induction of apoptosis by rWT virus. Additionally activation of proapoptotic BH3-only protein Bid through activation of caspase-8 also plays an important role. Finally, inactivation of both antiapoptotic proteins Mcl-1 and Bcl-XL is required. The inactivation of Mcl-1 involves loss of the protein due to inhibition of new host gene expression, while inactivation of Bcl-XL involves the activation of a BH3-only protein, presumably Bid. In the second part of my thesis I address the question of the dependence on the mitochondrial pathway of apoptosis induced by M protein mutant VSV. My results demonstrate that in HeLa cells, the mitochondrial pathway plays an important role in apoptosis and that once again Bak, Mcl-1 and Bcl-XL are involved. In the third part of my thesis I address the question of whether the stress-activated protein kinases (SAPKs) p38 and JNK play an important role in the induction of apoptosis by rWT virus. My results demonstrate that both SAPKs were activated during the time of induction of apoptosis, but inactivation of p38 or JNK did not affect the rate of the induction of apoptosis by rWT virus. Collectively, these results have shown that VSV activates multiple pathways, some of which are shared by both wildtype and M protein mutant viruses and others which are different.

subject

virology

apoptosis

contributor

Lyles, Douglas (committee chair)

Willingham, Mark (committee member)

McPhail, Linda (committee member)

Ornelles, David (committee member)

Wilkinson, John (committee member)

date

2009-06-04T15:41:50Z (accessioned)

2010-06-18T19:00:07Z (accessioned)

2009-06-04T15:41:50Z (available)

2010-06-18T19:00:07Z (available)

2009-06-04T15:41:50Z (issued)

degree

Molecular Genetics (discipline)

identifier

http://hdl.handle.net/10339/14924 (uri)

language

en (iso)

publisher

Wake Forest University

rights

Release the entire work immediately for access worldwide. (accessRights)

type

Thesis