Direct Detection of Diverse Metabolic Changes in Virally Transformed and Tax-Expressing Cells by Mass SpectrometryReport as inadecuate

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Viral transformation of a cell starts at the genetic level, followed by changes in the proteome and the metabolome of the host. There is limited information on the broad metabolic changes in HTLV transformed cells.

Methods and Principal Findings

Here, we report the detection of key changes in metabolites and lipids directly from human T-lymphotropic virus type 1 and type 3 HTLV1 and HTLV3 transformed, as well as Tax1 and Tax3 expressing cell lines by laser ablation electrospray ionization LAESI mass spectrometry MS. Comparing LAESI-MS spectra of non-HTLV1 transformed and HTLV1 transformed cells revealed that glycerophosphocholine PC lipid components were dominant in the non-HTLV1 transformed cells, and PCO-32∶1 and PCO-34∶1 plasmalogens were displaced by PC30∶0 and PC32∶0 species in the HTLV1 transformed cells. In HTLV1 transformed cells, choline, phosphocholine, spermine and glutathione, among others, were downregulated, whereas creatine, dopamine, arginine and AMP were present at higher levels. When comparing metabolite levels between HTLV3 and Tax3 transfected 293T cells, there were a number of common changes observed, including decreased choline, phosphocholine, spermine, homovanillic acid, and glycerophosphocholine and increased spermidine and N-acetyl aspartic acid. These results indicate that the lipid metabolism pathway as well as the creatine and polyamine biosynthesis pathways are commonly deregulated after expression of HTLV3 and Tax3, indicating that the noted changes are likely due to Tax3 expression. N-acetyl aspartic acid is a novel metabolite that is upregulated in all cell types and all conditions tested.

Conclusions and Significance

We demonstrate the high throughput in situ metabolite profiling of HTLV transformed and Tax expressing cells, which facilitates the identification of virus-induced perturbations in the biochemical processes of the host cells. We found virus type-specific HTLV1 vs. HTLV3, expression-specific Tax1 vs. Tax3 and cell-type–specific T lymphocytes vs. kidney epithelial cells changes in the metabolite profiles. The new insight on the affected metabolic pathways can be used to better understand the molecular mechanisms of HTLV induced transformation, which in turn can result in new treatment strategies.

Author: Prabhakar Sripadi, Bindesh Shrestha, Rebecca L. Easley, Lawrence Carpio, Kylene Kehn-Hall, Sebastien Chevalier, Renaud Mahieux, F



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