Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon
AUTOR(ES)
Greenwell-Wild, Teresa
FONTE
American Society of Hematology
RESUMO
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-α (IFN-α) 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-α 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-α 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-α and/or IFN-β, which in turn, induces APOBEC3, inhibited by IFN-α/β receptor blockade. In addition to macrophages, the IL-27–IFN-α connection is operative in CD4+ T cells, consistent with an IFN-α–dependent pathway underlying host cell defense to HIV.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2738572Documentos Relacionados
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