Hauber, Ilona Hofmann-Sieber, Helga Chemnitz, Jan Dubrau, Danilo Chusainow, Janet Stucka, Rolf Hartjen, Philip Schambach, Axel Ziegler, Patrick Hackmann, Karl Schröck, Evelin Schumacher, Udo Lindner, Christoph Grundhoff, Adam Baum, Christopher Manz, Markus G. Buchholz, Frank Hauber, Joachim 2013-09-26 Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2−/−γc−/− mice engrafted with either Tre-transduced primary CD4+ T cells, or Tre-transduced CD34+ hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV. application/pdf https://susi.usi.ch/global/documents/318975 https://localhost:5000/ark:/12658/srd1318975 https://susi.usi.ch/documents/318975/files/Hauber_PP_2013.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1003587 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318975 info:eu-repo/semantics/openAccess CC BY Plos pathogens. - 2013, vol. 9, no. 9, p. e1003587 info:eu-repo/classification/udc/61 Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice http://purl.org/coar/resource_type/c_6501