Type I interferon responses are impaired in latently HIV infected cells

FieldValue
dc.contributor.authorRanganath, Nischal
dc.contributor.authorSandstrom, Teslin S
dc.contributor.authorFadel, Saleh
dc.contributor.authorCôté, Sandra C
dc.contributor.authorAngel, Jonathan B
dc.date.accessioned2016-11-21T16:17:32Z
dc.date.available2016-11-21T16:17:32Z
dc.date.issued2016-09-09
dc.identifier.citationRetrovirology. 2016 Sep 09;13(1):66
dc.identifier.urihttp://dx.doi.org/10.1186/s12977-016-0302-9
dc.identifier.urihttp://hdl.handle.net/10393/35444
dc.description.abstractAbstract Background The latent HIV-1 reservoir represents the primary barrier to the eradication of HIV-1 infection. The design of novel reservoir-clearance strategies, however, is impeded in part by the inability to distinguish latently HIV-infected cells from uninfected cells. Significant impairment of the type I interferon (IFN-I) response is observed during productive HIV-1 infection. Although this remains poorly described in the context of latent HIV-1 infection, presence of potential defects may serve as a novel therapeutic target. Therefore, IFN-I pathways were characterized using two latently HIV-1-infected cell lines, U1 and OM10.1, in comparison to their respective uninfected parental U937 and HL60 cell lines. Findings Constitutive expression and induction of important mediators of IFN-I signaling including IFNα/β cytokines, IFNAR1, MHC-I, ISG15, and PKR were evaluated following exogenous IFNα or poly(I:C) treatment. Differences in basal expression of IFNAR1, MHC-I, and PKR were observed between the latently HIV-1 infected and uninfected cell lines. In parallel, significant impairments in the induction of MHC-I, ISG15 and PKR, as well as secretion of IFNα/β cytokines were observed in response to appropriate exogenous stimulation within the two latently HIV-infected U1 and OM10.1 cells, relative to their HIV-uninfected parental cells. Conclusions In comparison to the HIV-uninfected U937 and HL60 cell lines, widespread defects in IFN-I responsiveness were observed within the latently HIV-infected U1 and OM10.1 cells. These impairments represent novel therapeutic targets, which may be amenable to strategies currently employed in cancer therapy.
dc.titleType I interferon responses are impaired in latently HIV infected cells
dc.typeJournal Article
dc.date.updated2016-11-21T16:17:32Z
dc.language.rfc3066en
dc.rights.holderThe Author(s)
CollectionLibre accès - Publications // Open Access - Publications

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