Advertisement

 

 

Type I interferon responses are impaired in latently HIV infected cells.

Type I interferon responses are impaired in latently HIV infected cells.
Author Information (click to view)

Ranganath N, Sandstrom TS, Fadel S, Côté SC, Angel JB,


Ranganath N, Sandstrom TS, Fadel S, Côté SC, Angel JB, (click to view)

Ranganath N, Sandstrom TS, Fadel S, Côté SC, Angel JB,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Retrovirology 2016 09 0913(1) 66 doi 10.1186/s12977-016-0302-9

Abstract
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.

Submit a Comment

Your email address will not be published. Required fields are marked *

three + 19 =

[ HIDE/SHOW ]