Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes
1 Cancer Virology Program, University of Pittsburgh Cancer Institute Hillman Cancer Research Pavilion 5117 Centre Ave., Pittsburgh, PA 15213 USA
2 Cancer Biology Program, University of Wisconsin-Madison McArdle Laboratory for Cancer Research 1400 University Ave., Madison, WI 53706 USA
3 Biological Sciences Division and Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory, Environmental Molecular Sciences Laboratory 3335 Q Avenue, Richland, WA 99354 USA
BMC Genomics 2011, 12:625 doi:10.1186/1471-2164-12-625Published: 20 December 2011
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.
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.
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.