Nasopharyngeal carcinoma (NPC) is an epithelial malignancy which occurs at high incidence in endemic regions in Southern China, Northern Africa, and among Alaskan Eskimoes but also occurs worldwide in all populations. We have identified the viral sequences which encode RNA in tumor tissue and have identified specific viral transcripts from three regions of the EBV genome which are transcribed in NPC. We will determine when these transcripts are synthesized in lymphoid cell lines in vitro and in the NPC epithelial fusion cell line. NPC-KT. In order to further define which viral functions are expressed in malignant epithelial tissues we will use single-stranded RNA probes representing specific latent functions generated from vectors containing the SP6 and T7 bacteriophage promoters in Northern analyses or in nuclease protection assays. RNA preparations from NPC biopsy specimens an NPC which can be passaged in nude mice, C15, and the NPC cell line, NPC-KT will be compared to RNA from lymphoid cell lines. To facilitate a detailed analysis of viral transcription from the entire genome, we have constructed a cDNA library to NPC RNA in the vector, lambda gt11, by priming cDNA synthesis with oligo dT. Twelve viral specific clones have been identified. The viral cDNA structures will determined by restriction enzyme and sequence analysis. Additional libraries will be repeated from RNA from the same specimen and from additional NPC samples. In some instances cDNA will be primed with oligonucleotides for viraal genes. We will identify hyperplasias or other oropharyngeal malignancies associated with EBV by screening for EBV DNA. The structure of the viral termini will be analyzed to determine if the infected tissue produces linear virion DNA or contains only the episomal form. Monoclonal proliferations will be identified by this assay. Viral transcripts will be analyzed in the EBV-positive hyperplasias through the use of Northern blots, nuclease protection assays and cDNA cloning.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032979-06
Application #
3170879
Study Section
Experimental Virology Study Section (EVR)
Project Start
1983-06-01
Project End
1991-05-31
Budget Start
1990-04-01
Budget End
1991-05-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
DeKroon, Robert M; Gunawardena, Harsha P; Edwards, Rachel et al. (2018) Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A. MBio 9:
Marquitz, Aron R; Mathur, Anuja; Edwards, Rachel Hood et al. (2015) Host Gene Expression Is Regulated by Two Types of Noncoding RNAs Transcribed from the Epstein-Barr Virus BamHI A Rightward Transcript Region. J Virol 89:11256-68
Raab-Traub, Nancy (2015) Nasopharyngeal Carcinoma: An Evolving Role for the Epstein-Barr Virus. Curr Top Microbiol Immunol 390:339-63
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Fotheringham, Julie A; Raab-Traub, Nancy (2015) Epstein-Barr virus latent membrane protein 2 induces autophagy to promote abnormal acinus formation. J Virol 89:6940-4
Tworkoski, Kathryn; Raab-Traub, Nancy (2015) LMP1 promotes expression of insulin-like growth factor 1 (IGF1) to selectively activate IGF1 receptor and drive cell proliferation. J Virol 89:2590-602
Marquitz, Aron R; Mathur, Anuja; Chugh, Pauline E et al. (2014) Expression profile of microRNAs in Epstein-Barr virus-infected AGS gastric carcinoma cells. J Virol 88:1389-93
Fotheringham, Julie A; Raab-Traub, Nancy (2013) Epstein-Barr virus latent membrane protein 2 effects on epithelial acinus development reveal distinct requirements for the PY and YEEA motifs. J Virol 87:13803-15
Meckes Jr, David G; Gunawardena, Harsha P; Dekroon, Robert M et al. (2013) Modulation of B-cell exosome proteins by gamma herpesvirus infection. Proc Natl Acad Sci U S A 110:E2925-33
Meckes Jr, David G; Menaker, Nathan F; Raab-Traub, Nancy (2013) Epstein-Barr virus LMP1 modulates lipid raft microdomains and the vimentin cytoskeleton for signal transduction and transformation. J Virol 87:1301-11

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