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Cellular and viral determinants of m...

Golden, Joseph Walter.

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Cellular and viral determinants of mammalian reovirus uncoating.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Cellular and viral determinants of mammalian reovirus uncoating./
Author:	Golden, Joseph Walter.
Description:	205 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0086.
Contained By:	Dissertation Abstracts International66-01B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3161981
ISBN:	0496958682

Cellular and viral determinants of mammalian reovirus uncoating.
Golden, Joseph Walter.

Cellular and viral determinants of mammalian reovirus uncoating. - 205 p.

Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0086.

Thesis (Ph.D.)--University of Minnesota, 2005.

For non-enveloped viruses, the molecular determinants involved in converting an environmentally stable particle into a particle that can penetrate cellular membranes are not well understood. Productive infection by reovirus virions requires proteolytic degradation of the outer capsid protein sigma3 (virion uncoating). This proteolytic processing generates intermediate subvirion particles that are capable of penetrating cellular membranes. This thesis examined the cellular and viral requirements for sigma3 degradation. We found virion uncoating represents a critical determinant of reovirus cellular tropism and many cells that otherwise support replication cannot efficiently mediate this essential early step.

ISBN: 0496958682Subjects--Topical Terms:

1017734
Biology, Microbiology.

Cellular and viral determinants of mammalian reovirus uncoating.
LDR:03417nmm 2200313 4500 001 1818942
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020 $a 0496958682
035 $a (UnM)AAI3161981
035 $a AAI3161981
040 $a UnM $c UnM
100 1 $a Golden, Joseph Walter. $3 1908245
245 1 0 $a Cellular and viral determinants of mammalian reovirus uncoating.
300 $a 205 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0086.
500 $a Adviser: Leslie Ann Schiff.
502 $a Thesis (Ph.D.)--University of Minnesota, 2005.
520 $a For non-enveloped viruses, the molecular determinants involved in converting an environmentally stable particle into a particle that can penetrate cellular membranes are not well understood. Productive infection by reovirus virions requires proteolytic degradation of the outer capsid protein sigma3 (virion uncoating). This proteolytic processing generates intermediate subvirion particles that are capable of penetrating cellular membranes. This thesis examined the cellular and viral requirements for sigma3 degradation. We found virion uncoating represents a critical determinant of reovirus cellular tropism and many cells that otherwise support replication cannot efficiently mediate this essential early step.
520 $a The requirements for sigma3 degradation had been mostly characterized in fibroblasts. In these cells, sigma3 degradation requires the acid-dependent lysosomal cysteine proteases cathepsin (Cat) L and Cat B. Uncoating in fibroblasts requires acidic-pH, however, it was unknown whether acidic pH was required solely for the activity of acid-dependent proteases or if it also mediated another step in viral entry. Because both Cat L and B are expressed in many cell types, it was assumed these proteases facilitated reovirus infection in other cell types. We examined the requirements for uncoating in different cell types. Using protease inhibitors and cells engineered to express different lysosomal cysteine proteases, we demonstrated that Cat S can facilitate virion uncoating. Cat S facilitated reovirus infection in an acid-independent but strain-dependent fashion. We also investigated if the neutrophil-expressed serine protease neutrophil elastase (NE) could mediate sigma3 degradation. Using cells expressing NE and purified enzyme, we demonstrated that NE can facilitate sigma3 degradation. Infections facilitated by NE did not require acidic pH.
520 $a This thesis work expands our understanding of the cellular and viral determinants of virion uncoating and provides evidence that these factors contribute to reovirus tropism. Our findings show that distinct proteases can facilitate virion uncoating in different cell types. Our work demonstrates that the pH-sensitivity of sigma3 degradation reflects the requirements for protease activity and another early aspect of viral entry. Finally, this work sets the foundation for future studies that will examine how the requirement for cellular proteases can influence reovirus tissue tropism during natural infections.
590 $a School code: 0130.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Molecular. $3 1017719
690 $a 0410
690 $a 0379
690 $a 0307
710 2 0 $a University of Minnesota. $3 676231
773 0 $t Dissertation Abstracts International $g 66-01B.
790 1 0 $a Schiff, Leslie Ann, $e advisor
790 $a 0130
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3161981