Retroviral self-inactivation in the mouse vagina induced by short DNA.
Human immunodeficiency virus (HIV) has been shown to undergo self-destruction upon treatment of cell-free virions with partially double-stranded oligodeoxynucleotides targeting the polypurine tract (PPT) of the viral RNA in the virus particle. The ODN forms a local hybrid with the PPT activating the viral RNase H to prematurely cleave the genomic RNA. Here we are describing the self-destruction of a recombinant lentivirus harboring the PPT of HIV in a mouse vagina model. We showed a decrease in viral RNA levels in cell-free virus particles and a reduction reverse transcribed complementary DNA (cDNA) in virus-infected human and primary murine cells by incubation with ODNs. In the vagina simultaneous, prophylactic or therapeutic ODN treatments led to a significant reduction in viral RNA levels. Our finding may have some relevance for the design of other viral self-destruction approaches. It may lead to a microbicide for reduction of sexual and mother-to-child transmission.
Wittmer-Elzaouk
Lina
L
Institute of Medical Virology, University of Zurich, Gloriastrasse 30/32, CH-8006 Zurich, Switzerland.
Jung-Shiu
Jiunshan
J
Heinrich
Jochen
J
Moelling
Karin
K
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects / Q000821:virology*; D038301:Virus Inactivation / Q000187:drug effects*
D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides