Research abstract
Letter abstract
Nature Biotechnology 25, 669 - 674 (2007)
Published online: 3 June 2007 | doi:10.1038/nbt1311
RNase H-mediated retrovirus destruction in vivo triggered by oligodeoxynucleotides
Kathrin Matzen1,2,3, Lina Elzaouk1,3, Alexey A Matskevich1,3, Anja Nitzsche2, Jochen Heinrich1 & Karin Moelling1
Abstract
The HIV-1 RNase H can be prematurely activated by oligodeoxynucleotides targeting the highly conserved polypurine tract required for second strand DNA synthesis1, 2, 3, 4, 5. This inhibits retroviral replication in cell-free HIV particles and newly infected cells1, 2, 3, 4. Here we extend these studies to an in vivo model of retroviral replication. Mice that are chronically infected with the spleen focus-forming virus and treated with oligodeoxynucleotides that target the polypurine tract, exhibit either transient or long-term reductions in plasma virus titer, depending on the therapeutic regimen. Treatment prior to, during or shortly after infection can delay disease progression, increase survival rates and prevent viral infection. This strategy destroys viral RNA template in virus particles in serum as well as early retroviral replication intermediates in infected cells. As it targets events common to the replication cycle of all retroviruses, this approach may be broadly applicable to retroviruses of medical and agricultural importance.
- Institute of Medical Virology, University of Zurich, Gloriastrasse 30, 8006 Zurich, Switzerland.
- Present addresses: Karlstrasse 41, 80333 Munich, Germany (K.M.) and Elswigstrasse 68, 23562 Lubeck, Germany (A.N.).
- These authors contributed equally to this work.
Correspondence to: Karin Moelling1 e-mail: moelling@immv.unizh.ch
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