Recombination of Retrotransposon and Exogenous RNA Virus Results in Nonretroviral cDNA Integration
Markus B. Geuking,1*
Jacqueline Weber,1
Marie Dewannieux,2
Elieser Gorelik,3
Thierry Heidmann,2
Hans Hengartner,1
Rolf M. Zinkernagel,1
Lars Hangartner1||
Retroviruses have the potential to acquire host cell–derived
genetic material during reverse transcription and can integrate
into the genomes of larger, more complex DNA viruses. In contrast,
RNA viruses were believed not to integrate into the host's genome
under any circumstances. We found that illegitimate recombination
between an exogenous nonretroviral RNA virus, lymphocytic choriomeningitis
virus, and the endogenous intracisternal A-type particle (IAP)
retrotransposon occurred and led to reverse transcription of
exogenous viral RNA. The resulting complementary DNA was integrated
into the host's genome with an IAP element. Thus, RNA viruses
should be closely scrutinized for any capacity to interact with
endogenous retroviral elements before their approval for therapeutic
use in humans.
2 CNRS Unité Mixte de Recherche 8122, Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Institut Gustave Roussy, 94805 Villejuif Cedex and Université Paris-Sud 91405 Orsay, France.
3 University of Pittsburgh Cancer Institute, Hillman Cancer Center, Room 1.46, Pittsburgh, PA 15232, USA.
* Present address: Department of Medicine, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Present address: Institut für Molekulare Biomedizin, ETH Zürich, Wagistrasse 27, 8952 Schlieren, Switzerland.
These authors contributed equally to this work.
|| Present address: Institute of Medical Virology, University of Zurich, Gloriastrasse 30, 8006 Zurich, Switzerland.
To whom correspondence should be addressed. E-mail: hangartner.lars{at}virology.uzh.ch (L.H.); geuking{at}mcmaster.ca (M.B.G.); rolf.zinkernagel{at}usz.ch (R.M.Z.)
