U.S. Department of Energy

Pacific Northwest National Laboratory

Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes.

TitleCoupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes.
Publication TypeJournal Article
Year of Publication2011
AuthorsDresang LR, Teuton JR, Feng H, Jacobs JM, Camp DG, Purvine SO, Gritsenko MA, Li Z, Smith RD, Sugden B, Moore PS, Chang Y
JournalBMC Genomics
KeywordsGenes, Viral, Herpesvirus 4, Human, Herpesvirus 8, Human, Humans, Mass Spectrometry, Proteome, Transcriptome
Abstract

BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions.

RESULTS: The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels.

CONCLUSIONS: This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

DOI10.1186/1471-2164-12-625
Alternate JournalBMC Genomics
PubMed ID22185355
PubMed Central IDPMC3282826
Grant ListCA070723 / CA / NCI NIH HHS / United States
CA120726 / CA / NCI NIH HHS / United States
CA133027 / CA / NCI NIH HHS / United States
CA136363 / CA / NCI NIH HHS / United States
P01 CA022443 / CA / NCI NIH HHS / United States
P41 RR018522 / RR / NCRR NIH HHS / United States
P41 RR018522-09 / RR / NCRR NIH HHS / United States
RR018522 / RR / NCRR NIH HHS / United States
T32 AI060525 / AI / NIAID NIH HHS / United States
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