Tools

LEADER 04352nam 2200541Ii 4500

001 ocn936213493;

003 OCoLC;

005 20160329120808.0;

006 m o d ;

007 cr unu||||||||;

008 160129s2015 ncua ob 000 0 eng d;

035 a| (Sirsi) o936213493;

035 a| (OCoLC)936213493;

049 a| EREE;

090 a| QR400;

100 1 a| Walker, Lia R.,e| author.?| UNAUTHORIZED;

245 10 a| Function of disintegrin-like domain of KSHV gB in regulating virus infection /c| by Lia R. Walker.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2015.;

300 a| 163 pages :b| illustrations (some color);

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 2.92 MB2| rda;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph.D.c| East Carolina Universityd| 2015.;

500 a| Presented to the faculty of the Interdisciplinary Doctoral Program in Biological Sciences.;

500 a| Advisor: Shaw M. Akula.;

500 a| Title from PDF t.p. (viewed March 2, 2016).;

504 a| Includes bibliographical references.;

520 3 a| KSHV, also referred to as human herpesvirus-8 (HHV-8), is the eighth and latest identified human herpesvirus. It is the causative agent for a variety of malignancies namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). The processes and mechanisms involved in virus entry are among the many intricacies not fully understood regarding KSHV and other viruses. As in other herpesviruses, KSHV target cell entry is a complex process consisting of multiple steps which include: initial attachment/binding to the cell, virus:cell surface receptor interactions, virus internalization/uptake, and subsequent trafficking of the virus for nuclear delivery. Viral envelope glycoproteins interact with target cell surface receptor molecules to facilitate entry into cells. For instance, virus envelope associated glycoprotein B (gB) of KSHV is known to interact with integrins via its RGD (Arg-Gly-Asp; 27-29aa) integrin binding domain. RGD of KSHV functionally interacts with integrins [alpha]3[beta]1, [alpha]V[beta]3, and [alpha]V[beta]5 that have a role in initiating internalization. Cell surface receptors, like integrins, aid in a virus' ability to establish a successful infection. In addition to RGD, KSHV gB also harbors the lesser studied integrin recognition motif, disintegrin-like domain (DLD; 66-85aa). As it pertains to virus entry in general, few studies have sought to establish a role for DLD, which is highly conserved among gB homologs. In the following studies, we employed phage display peptide library screening and recombinant viruses to determine that DLD of KSHV gB binds [alpha]9[beta]1 integrin on the surface of target cells in an interaction critical for infection. We go on to specify a role for DLD-binding [alpha]9[delta]1 in mediating KSHV entry by employing subcellular fractionation. The virus interactions with [alpha]9[beta]1 are crucial for endosomal trafficking of KSHV, as integrin [alpha]9[beta]1 was observed to have a role in late endosomal escape of KSHV for cytosolic delivery. These studies provide new insights in regards to KSHV infectious entry into target cells. Advancing our knowledge of virus entry is critical for a thorough understanding of KSHV pathogenesis.;

650 0 a| Herpesviruses.=| ^A144272;

650 0 a| Virusesx| Receptors.=| ^A1288605;

653 a| disintegrin-like domain;

653 a| disintegrins;

653 a| integrins;

700 1 a| Akula, Shaw M.,e| degree supervisor.=| ^A1406820;

710 2 a| East Carolina University.b| Department of Biology.=| ^A637467;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/5123;

949 a| Click on web addressw| ASISh| JOYNER101;

949 a| Click on web addressw| ASISh| HSL111;

949 o| wjh;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 4356310;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4356310-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 1/29/2016x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4356310-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 1/29/2016x| ETDz| HERESOURCE;

Function of disintegrin-like domain of KSHV gB in regulating virus infection / by Lia R. Walker.

Author/creator	Walker, Lia R. author.
Other author	Akula, Shaw M., degree supervisor.
Other author	East Carolina University. Department of Biology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2015.
Description	163 pages : illustrations (some color)
Supplemental Content	Access via ScholarShip
Subjects	Herpesviruses. Viruses--Receptors.

Summary	KSHV, also referred to as human herpesvirus-8 (HHV-8), is the eighth and latest identified human herpesvirus. It is the causative agent for a variety of malignancies namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). The processes and mechanisms involved in virus entry are among the many intricacies not fully understood regarding KSHV and other viruses. As in other herpesviruses, KSHV target cell entry is a complex process consisting of multiple steps which include: initial attachment/binding to the cell, virus:cell surface receptor interactions, virus internalization/uptake, and subsequent trafficking of the virus for nuclear delivery. Viral envelope glycoproteins interact with target cell surface receptor molecules to facilitate entry into cells. For instance, virus envelope associated glycoprotein B (gB) of KSHV is known to interact with integrins via its RGD (Arg-Gly-Asp; 27-29aa) integrin binding domain. RGD of KSHV functionally interacts with integrins [alpha]3[beta]1, [alpha]V[beta]3, and [alpha]V[beta]5 that have a role in initiating internalization. Cell surface receptors, like integrins, aid in a virus' ability to establish a successful infection. In addition to RGD, KSHV gB also harbors the lesser studied integrin recognition motif, disintegrin-like domain (DLD; 66-85aa). As it pertains to virus entry in general, few studies have sought to establish a role for DLD, which is highly conserved among gB homologs. In the following studies, we employed phage display peptide library screening and recombinant viruses to determine that DLD of KSHV gB binds [alpha]9[beta]1 integrin on the surface of target cells in an interaction critical for infection. We go on to specify a role for DLD-binding [alpha]9[delta]1 in mediating KSHV entry by employing subcellular fractionation. The virus interactions with [alpha]9[beta]1 are crucial for endosomal trafficking of KSHV, as integrin [alpha]9[beta]1 was observed to have a role in late endosomal escape of KSHV for cytosolic delivery. These studies provide new insights in regards to KSHV infectious entry into target cells. Advancing our knowledge of virus entry is critical for a thorough understanding of KSHV pathogenesis.
General note	Presented to the faculty of the Interdisciplinary Doctoral Program in Biological Sciences.
General note	Advisor: Shaw M. Akula.
General note	Title from PDF t.p. (viewed March 2, 2016).
Dissertation note	Ph.D. East Carolina University 2015.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Availability

Library	Location	Call Number	Status	Item Actions
	Electronic Resources	Access Content Online	✔ Available

Function of disintegrin-like domain of KSHV gB in regulating virus infection / by Lia R. Walker.

Click here for more information about this title

Availability