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035 a| (Sirsi) o988775894;

035 a| (OCoLC)988775894;

049 a| EREE;

100 1 a| Fazio-Kroll, Ana Laura,e| author.?| UNAUTHORIZED;

245 10 a| Novel role of Human T-cell leukemia virus type-1 encoded protein HBZ in viral transmission through cell-to-cell contact /c| by Ana Laura Fazio-Kroll.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2017.;

300 a| 170 pages :b| color illustrations.;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 3.94 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

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

502 b| Ph.D.c| East Carolina Universityd| 2017.;

500 a| Presented to the faculty of the Department of Microbiology and Immunology.;

500 a| Advisor: Isabelle Lemasson.;

500 a| Title from PDF t.p. (viewed July 26, 2017).;

520 3 a| The complex retrovirus Human T cell leukemia virus type I (HTLV-1) is the etiologic agent of several diseases, including Adult T cell leukemia (ATL), a fatal hematological malignancy that affects mainly CD4+ T-cells. Freshly isolated ATL and HTLV-1 infected cells aggregate spontaneously in vitro. We have observed this same phenotype in T-cells exclusively expressing one of the viral proteins called HTLV-1 basic leucine zipper factor (HBZ). The hbz gene is uniquely encoded by the complementary strand of the HTLV-1 provirus and, in contrast to other HTLV-1 proteins, is constitutively expressed in ATL and HTLV-1-infected cells. High levels of aggregation in ATL cells have been correlated to an upregulation of the intercellular adhesion molecule-1 (ICAM-1). This protein is usually activated after T-cell stimulation and plays an important role in forming and stabilizing the immunological synapse. Interestingly, we found that cells expressing HBZ have an increase in ICAM-1 mRNA, which correlates with an increase in ICAM-1 at the cell surface. We confirmed by luciferase assay that HBZ expression stimulates ICAM-1 transcription. We found that blocking antibodies or peptides against ICAM-1 and its ligand, lymphocyte function-associated antigen 1 (LFA-1), dissociate the aggregates formed by HBZ-expressing cells, suggesting that ICAM-1 overexpression by HBZ mediates T-cell aggregation through interaction with LFA-1. Increased ICAM-1 expression at the cell surface is crucial for the formation of cell-to-cell contacts and efficient HTLV-1 transmission. To determine whether overexpression of ICAM-1 by HBZ plays a role in viral spread, we performed infection assays using a single-cycle, replication dependent reporter system. Interestingly, we found that HBZ expression significantly enhances HTLV-1 transmission. We confirmed that this effect involves the presence of LFA-1 on target cells. In addition, blocking the ICAM-1/LFA-1 interaction with an ICAM-1 antibody significantly reduced viral transmission. Therefore, ICAM-1 overexpression by HBZ plays a role in mediating viral transmission in our assays. A better understanding of the mechanisms used by HBZ to upregulate ICAM-1, induce cell-to-cell contact, and enhance virus transmission is important for future efforts to limit viral spread and prevent diseases in HTLV-1-infected individuals.;

504 a| Includes bibliographical references.;

650 2 a| Human T-lymphotropic virus 1.=| ^A1037506;

650 2 a| Protein HBZ.?| UNAUTHORIZED;

650 2 a| Viral transmission.?| UNAUTHORIZED;

700 1 a| Lemasson, Isabelle,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Microbiology and Immunology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/6200;

949 o| wjh;

994 a| C0b| ERE;

096 a| QW 168.5.R18;

596 a| 1 4;

998 a| 4704203;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4704203-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 6/2/2017x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4704203-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 6/2/2017x| ETDz| HERESOURCE;

Novel role of Human T-cell leukemia virus type-1 encoded protein HBZ in viral transmission through cell-to-cell contact / by Ana Laura Fazio-Kroll.

Author/creator	Fazio-Kroll, Ana Laura author.
Other author	Lemasson, Isabelle, degree supervisor.
Other author	East Carolina University. Department of Microbiology and Immunology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2017.
Description	170 pages : color illustrations.
Supplemental Content	Access via ScholarShip
Subjects	Human T-lymphotropic virus 1. Protein HBZ. Viral transmission.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	The complex retrovirus Human T cell leukemia virus type I (HTLV-1) is the etiologic agent of several diseases, including Adult T cell leukemia (ATL), a fatal hematological malignancy that affects mainly CD4+ T-cells. Freshly isolated ATL and HTLV-1 infected cells aggregate spontaneously in vitro. We have observed this same phenotype in T-cells exclusively expressing one of the viral proteins called HTLV-1 basic leucine zipper factor (HBZ). The hbz gene is uniquely encoded by the complementary strand of the HTLV-1 provirus and, in contrast to other HTLV-1 proteins, is constitutively expressed in ATL and HTLV-1-infected cells. High levels of aggregation in ATL cells have been correlated to an upregulation of the intercellular adhesion molecule-1 (ICAM-1). This protein is usually activated after T-cell stimulation and plays an important role in forming and stabilizing the immunological synapse. Interestingly, we found that cells expressing HBZ have an increase in ICAM-1 mRNA, which correlates with an increase in ICAM-1 at the cell surface. We confirmed by luciferase assay that HBZ expression stimulates ICAM-1 transcription. We found that blocking antibodies or peptides against ICAM-1 and its ligand, lymphocyte function-associated antigen 1 (LFA-1), dissociate the aggregates formed by HBZ-expressing cells, suggesting that ICAM-1 overexpression by HBZ mediates T-cell aggregation through interaction with LFA-1. Increased ICAM-1 expression at the cell surface is crucial for the formation of cell-to-cell contacts and efficient HTLV-1 transmission. To determine whether overexpression of ICAM-1 by HBZ plays a role in viral spread, we performed infection assays using a single-cycle, replication dependent reporter system. Interestingly, we found that HBZ expression significantly enhances HTLV-1 transmission. We confirmed that this effect involves the presence of LFA-1 on target cells. In addition, blocking the ICAM-1/LFA-1 interaction with an ICAM-1 antibody significantly reduced viral transmission. Therefore, ICAM-1 overexpression by HBZ plays a role in mediating viral transmission in our assays. A better understanding of the mechanisms used by HBZ to upregulate ICAM-1, induce cell-to-cell contact, and enhance virus transmission is important for future efforts to limit viral spread and prevent diseases in HTLV-1-infected individuals.
General note	Presented to the faculty of the Department of Microbiology and Immunology.
General note	Advisor: Isabelle Lemasson.
General note	Title from PDF t.p. (viewed July 26, 2017).
Dissertation note	Ph.D. East Carolina University 2017.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Novel role of Human T-cell leukemia virus type-1 encoded protein HBZ in viral transmission through cell-to-cell contact / by Ana Laura Fazio-Kroll.

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