Torque teno virus 10 isolated by genome amplification techniques from a patient with concomitant chronic lymphocytic leukemia and polycythemia vera

An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers o...

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Bibliographic Details
Published in:Molecular medicine (Cambridge, Mass.) Mass.), 2011-11, Vol.17 (11-12), p.1338-1348
Main Authors: Chu, Charles C, Zhang, Lu, Dhayalan, Arjun, Agagnina, Briana M, Magli, Amanda R, Fraher, Gia, Didier, Sebastien, Johnson, Linda P, Kennedy, William J, Damle, Rajendra N, Yan, Xiao-Jie, Patten, Piers E M, Teichberg, Saul, Koduru, Prasad, Kolitz, Jonathan E, Allen, Steven L, Rai, Kanti R, Chiorazzi, Nicholas
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Blood Donors
Case-Control Studies
DNA Virus Infections - blood
DNA Virus Infections - complications
DNA Virus Infections - virology
DNA, Viral - blood
DNA, Viral - genetics
Female
Genome, Viral - genetics
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - blood
Leukemia, Lymphocytic, Chronic, B-Cell - complications
Leukemia, Lymphocytic, Chronic, B-Cell - virology
Male
Middle Aged
Nucleic Acid Amplification Techniques - methods
Polycythemia Vera - blood
Polycythemia Vera - complications
Polycythemia Vera - virology
Reproducibility of Results
Torque teno virus - genetics
Torque teno virus - isolation & purification
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Summary:An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility. Using genome amplification methods, we identified a new isolate (BIS8-17) of torque teno virus (TTV) 10. The presence of blood isolate sequence 8-17 (BIS8-17) in the original plasma was confirmed by polymerase chain reaction (PCR), validating the approach, since TTV is a known plasma virus. Subsequent PCR testing of plasmas from additional patients showed that BIS8-17 had a similar incidence (~20%) in CLL (n = 48) or PV (n = 10) compared with healthy controls (n = 52). CLL cells do not harbor BIS8-17; PCR did not detect it in CLL peripheral blood genomic deoxyribonucleic acid (DNA) (n = 20). CLL patient clinical outcome or prognostic markers (immunoglobulin heavy chain variable region [IGHV ] mutation, CD38 or zeta-chain associated protein kinase 70 kDa [ZAP-70]) did not correlate with BIS8-17 infection. Although not causative to our knowledge, this is the first reported isolation and detection of TTV in either CLL or PV. TTV could serve as a covirus with another infectious agent or TTV variant with rearranged genetic components that contribute to disease pathogenesis. These results prove that this method identifies infectious agents and provides an experimental methodology to test correlation with disease.
ISSN:1076-1551
1528-3658
DOI:10.2119/molmed.2010.00110