title: Torque teno virus 10 isolated by genome amplification techniques from a patient with concomitant chronic lymphocytic leukemia and polycythemia vera.
abstract: 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.
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish-LIJ Health System, Manhasset, New York, United States of America. cchu@nshs.edu
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chu
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Arjun
authors.initials: A
authors.lastname: Dhayalan
authors.forename: Briana M
authors.initials: BM
authors.lastname: Agagnina
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Magli
authors.forename: Gia
authors.initials: G
authors.lastname: Fraher
authors.forename: Sebastien
authors.initials: S
authors.lastname: Didier
authors.forename: Linda P
authors.initials: LP
authors.lastname: Johnson
authors.forename: William J
authors.initials: WJ
authors.lastname: Kennedy
authors.forename: Rajendra N
authors.initials: RN
authors.lastname: Damle
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Yan
authors.forename: Piers E M
authors.initials: PE
authors.lastname: Patten
authors.forename: Saul
authors.initials: S
authors.lastname: Teichberg
authors.forename: Prasad
authors.initials: P
authors.lastname: Koduru
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Steven L
authors.initials: SL
authors.lastname: Allen
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001782:Blood Donors; D016022:Case-Control Studies; D004266:DNA Virus Infections / Q000097:blood / Q000150:complications / Q000821:virology; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D016679:Genome, Viral / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000150:complications* / Q000821:virology; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011087:Polycythemia Vera / Q000097:blood / Q000150:complications* / Q000821:virology*; D015203:Reproducibility of Results; D022783:Torque teno virus / Q000235:genetics* / Q000302:isolation & purification*
chemical_list: D004279:DNA, Viral