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The replicative activity of human endogenous retrovirus K102 (HERV-K102) with HIV viremia

Laderoute, Marian Pa,b; Giulivi, Antonioa,b; Larocque, Louisea; Bellfoy, Deanaa; Hou, Yangxuna; Wu, Hong-Xinga; Fowke, Keithc; Wu, Juna; Diaz-Mitoma, Franciscod

doi: 10.1097/QAD.0b013e3282f14d64
Basic Science

Objective: To address the activation and replicative activity of HERV-K102 in vivo associated with HIV viremia.

Design and Methods: Initially serology was performed on HERV-K102 specific envelope peptides to determine if HERV-K102 may become activated with HIV viremia. Before developing a quantitative PCR (qPCR) assay, we first determined whether plasma associated particles contained DNA or RNA genomes in a pilot study which surprisingly revealed predominantly DNA genomes. A relative, ddCt qPCR ratio method was then devised to detect excess levels of HERV-K102 pol DNA templates over genomic levels which served as a surrogate marker to reliably index the level of particles found in plasma.

Results: Both the peptide serology and ddCt qPCR excess ratio methods suggested the activation of HERV-K102 in about 70–80% of HIV viremic cases whereas only 2–3% of normal healthy adults had marginally activated HERV-K102 (P < 0.0001). Moreover, by digestion with dUTPase we were able to confirm that the vast majority of excess DNA template in plasma related to cDNA production rather than representing genomic copies.

Conclusions: Our work uniquely suggests the common activation of HERV-K102 with HIV viremia and may be first to directly demonstrate HERV-K102 cDNA production in vivo. The potential implications of the induction of HERV-K102 activation and replication for the prevention and control of HIV are discussed.

From the aBloodborne Pathogens Section, Blood Safety Surveillance and Healthcare Acquired Infections Division, Centre for Infectious Disease Prevention and Control, Public Health Agency of Canada, Ottawa, Ontario, Canada

bDepartment of Pathology and Laboratory Medicine, University of Ottawa, Ontario, Canada

cDepartment of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

dDivision of Virology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.

Received 5 March, 2007

Revised 30 June, 2007

Accepted 7 August, 2007

Correspondence to M.P. Laderoute, Public Health Agency of Canada, AL 060 1E2 Tunney's Pasture, Ottawa, Ontario Canada K1A 0K9. Tel: +1 613 957 9568; fax: +1 613 954 2354; e-mail: marian_p_laderoute@hc-sc.gc.ca

© 2007 Lippincott Williams & Wilkins, Inc.