By interfering with the type I interferon (IFN1) response, human immunodeficiency virus 1 (HIV-1) can circumvent host antiviral signalling and establish persistent viral reservoirs. HIV-1-mediated defects in the IFN pathway are numerous, and include the impairment of protein receptors involved in pathogen detection, downstream signalling cascades required for IFN1 upregulation, and expression or function of key IFN1-inducible, antiviral proteins. Despite this, the activation of IFN1-inducible, antiviral proteins has been shown to facilitate the killing of latently HIV-infected cells in vitro. Understanding how IFN1 signalling is blocked in physiologically-relevant models of HIV-1 infection, and whether these defects can be reversed, is therefore of great importance for the development of novel therapeutic strategies aimed at eradicating the HIV-1 reservoir.

The inability to sample deep-tissue reservoirs in individuals living with human immunodeficiency virus (HIV) has greatly hindered accurate estimates of viral reservoir size and distribution. Animal models and collection of tissues during autopsies of HIV-positive individuals are 2 proposed solutions to this problem. Each, however, has its limitations. In this Viewpoint, we argue that tissue donation following medical assistance in death (MAiD) will form an invaluable resource for the characterization of the viral reservoir in the context of current HIV cure research. In support, we discuss a recent instance in which an individual living with HIV chose to donate their body/tissues to HIV research prior to undergoing MAiD at our institution. Going forward, we hope this will help provide support to individuals in their decisions around tissue donation following MAiD, while highlighting how healthcare providers, by complying with such wishes, can affect patient satisfaction in the last days of life.

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.FindingsConstitutive 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0302-9) contains supplementary material, which is available to authorized users.