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003 OCoLC;

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008 180529s2018 ncua obm 000 0 eng d;

035 a| (Sirsi) o1037952039;

035 a| (OCoLC)1037952039;

049 a| EREE;

100 1 a| Hussein, Hosni Ahmed Mohamed,e| author.?| UNAUTHORIZED;

245 10 a| Micronome and KSHV infection :b| identification and functional characterization of cellular microRNAs during virus entry /c| by Hosni Ahmed Mohamed Hussein.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2018.;

300 a| 149 pages :b| illustrations (chiefly color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 2.19 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

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

500 a| Advisor: Shaw M. Akula;

500 a| Title from PDF t.p. (viewed July 24, 2018).;

538 a| System requirements: Adobe Reader.;

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

502 b| Ph.D.c| East Carolina Universityd| 2018.;

520 3 a| Kaposi's sarcoma-associated herpesvirus (KSHV), is the most recently identified human herpesvirus and causes a variety of human malignancies. KSHV is etiologically associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). MicroRNAs (miRNAs) are small non-coding RNA molecules that play important post transcriptional regulatory roles in gene expression and can greatly influence virus-host cell interactions. KSHV is one of a few examples of viruses that encode their own miRNAs. KSHV encodes 12 pre-miRNAs which are processed to yield 25 mature miRNAs. To date, extensive work has been conducted on the expression and roles of cellular and KSHV-encoded miRNAs during virus latency, replication, and angiogenesis. However, little is currently known about the roles of microRNAs (miRNAs) in KSHV entry. In the following studies, we investigated the induction of cellular miRNA expression in response to initial stages of KSHV infection and their roles in virus entry. We employed deep sequencing to analyze miRNA expression in KSHV infected BJAB cells at 15min post infection (PI) and compared this to uninfected BJAB cells. The expression profile of cellular miRNAs was significantly altered in response to KSHV entry. Interestingly, expression of these KSHV-induced miRNAs noted during early stages of infection does not require virus replication, as UV-inactivated KSHV could induce the expression of cellular miRNAs to comparable levels as live wild-type KSHV. A synthetic mimic for miR-36, a novel cellular miRNA expressed in response to KSHV infection, was able to significantly inhibit virus entry by targeting the expression of interferon induced transmembrane protein 1 (IFITM1). The effect of miR-36 on KSHV infection of cells was at a post-binding stage of virus entry. Similarly, miR-36 mimic inhibits infection of closely related DNA viruses: Epstein-Barr virus (EBV), and herpes simplexvirus-2 (HSV-2). IFITM1 was observed to have a crucial role in the in vitro and in vivo infection of gammaherpesviruses. IFITM1-specific siRNA inhibits gammaherpesviruses infection in BJAB cells and BALB/c mice. Taken together, our studies provide new insights and appreciation for the role of the host cellular miRNAs to inhibit internalization of KSHV which may contribute to the development of miRNA-based antiviral therapy.;

504 a| Includes bibliographical references.;

650 2 a| MicroRNAs.=| ^A1032967;

650 2 a| Sarcoma, Kaposi.=| ^A964398;

650 2 a| Herpesvirus 8, Human.=| ^A947360;

650 2 a| Virus Internalization.=| ^A1362249;

650 2 a| Cell Line.=| ^A919245;

653 a| Kaposi's sarcoma & IFITM1;

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

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/10342/6755;

949 o| wjh;

994 a| C0b| ERE;

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596 a| 1 4;

998 a| 4867539;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4867539-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 5/31/2018x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4867539-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 5/31/2018x| ETDz| HERESOURCE;

Micronome and KSHV infection : identification and functional characterization of cellular microRNAs during virus entry / by Hosni Ahmed Mohamed Hussein.

Author/creator	Hussein, Hosni Ahmed Mohamed author.
Other author	Akula, Shaw M., degree supervisor.
Other author	East Carolina University. Department of Microbiology and Immunology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2018.
Description	149 pages : illustrations (chiefly color).
Supplemental Content	Access via ScholarShip
Subjects	MicroRNAs. Sarcoma, Kaposi. Herpesvirus 8, Human. Virus Internalization. Cell Line.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Kaposi's sarcoma-associated herpesvirus (KSHV), is the most recently identified human herpesvirus and causes a variety of human malignancies. KSHV is etiologically associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). MicroRNAs (miRNAs) are small non-coding RNA molecules that play important post transcriptional regulatory roles in gene expression and can greatly influence virus-host cell interactions. KSHV is one of a few examples of viruses that encode their own miRNAs. KSHV encodes 12 pre-miRNAs which are processed to yield 25 mature miRNAs. To date, extensive work has been conducted on the expression and roles of cellular and KSHV-encoded miRNAs during virus latency, replication, and angiogenesis. However, little is currently known about the roles of microRNAs (miRNAs) in KSHV entry. In the following studies, we investigated the induction of cellular miRNA expression in response to initial stages of KSHV infection and their roles in virus entry. We employed deep sequencing to analyze miRNA expression in KSHV infected BJAB cells at 15min post infection (PI) and compared this to uninfected BJAB cells. The expression profile of cellular miRNAs was significantly altered in response to KSHV entry. Interestingly, expression of these KSHV-induced miRNAs noted during early stages of infection does not require virus replication, as UV-inactivated KSHV could induce the expression of cellular miRNAs to comparable levels as live wild-type KSHV. A synthetic mimic for miR-36, a novel cellular miRNA expressed in response to KSHV infection, was able to significantly inhibit virus entry by targeting the expression of interferon induced transmembrane protein 1 (IFITM1). The effect of miR-36 on KSHV infection of cells was at a post-binding stage of virus entry. Similarly, miR-36 mimic inhibits infection of closely related DNA viruses: Epstein-Barr virus (EBV), and herpes simplexvirus-2 (HSV-2). IFITM1 was observed to have a crucial role in the in vitro and in vivo infection of gammaherpesviruses. IFITM1-specific siRNA inhibits gammaherpesviruses infection in BJAB cells and BALB/c mice. Taken together, our studies provide new insights and appreciation for the role of the host cellular miRNAs to inhibit internalization of KSHV which may contribute to the development of miRNA-based antiviral therapy.
General note	Presented to the faculty of the Department of Microbiology and Immunology
General note	Advisor: Shaw M. Akula
General note	Title from PDF t.p. (viewed July 24, 2018).
Dissertation note	Ph.D. East Carolina University 2018.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Micronome and KSHV infection : identification and functional characterization of cellular microRNAs during virus entry / by Hosni Ahmed Mohamed Hussein.

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