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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1864-1874. Prepublished online as a Blood First Edition Paper on June 25, 2009; DOI 10.1182/blood-2009-03-211540. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2009-03-211540v1 114/9/1864    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Greenwell-Wild, T. Articles by Wahl, S. M. PubMed PubMed Citation Articles by Greenwell-Wild, T. Articles by Wahl, S. M. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon Teresa Greenwell-Wild1, Nancy Vázquez1, Wenwen Jin1, Zoila Rangel2, Peter J. Munson2, and Sharon M. Wahl1 1 Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research; and 2 Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD Infection of CD4+ chemokine coreceptor+ targets by HIV is aided and abetted by the proficiency of HIV in eliminating or neutralizing host cell–derived defensive molecules. Among these innate protective molecules, a family of intracellular apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases, is constitutively expressed but inactivated by HIV viral infectivity factor. The ability of interferon- (IFN-) to augment cytidine deaminases offered the possibility that the balance between virus and target cell might be altered in favor of the host. Further characterization of transcriptional profiles induced by IFN- using microarrays, with the intention to identify and dissociate retroviral countermaneuvers from associated toxicities, revealed multiple molecules with suspected antiviral activity, including IL-27. To establish whether IFN- toxicity might be sidestepped through the use of downstream IL-27 against HIV, we examined whether IL-27 directly regulated cytidine deaminases. Although IL-27 inducesAPOBECs, it does so in a delayed fashion. Dissecting the underlying regulatory events uncovered an initial IL-27–dependent induction of IFN- and/or IFN-β, which in turn, induces APOBEC3, inhibited by IFN-/β receptor blockade. In addition to macrophages, the IL-27–IFN- connection is operative in CD4+ T cells, consistent with an IFN-–dependent pathway underlying host cell defense to HIV. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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