KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.

Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.

'I had to tell my GP I had lung cancer': patient perspectives of hospital- and community-based lung cancer care.

Lung cancer care spans both hospital- and community-based healthcare settings, and suboptimal communication between healthcare providers impacts on continuity and quality of care. Patients' experiences regarding: (1) communication between healthcare providers; and (2) the role of their GP during cancer treatment was explored in interviews with 47 Western Australian lung cancer patients. Thematic analysis using a phenomenological approach was undertaken to derive key themes regarding participant experiences. Poor communication between hospital cancer specialists (HCSs) influenced participants' treatment choices and perceptions of the quality of their care. Information provided by HCSs to GPs was often delayed or incomplete, and many participants perceived themselves as a messenger between healthcare settings. Participants' opinions about the GP role during cancer treatment ranged from 'no role' to an 'active member of the treating team'. A new model of cancer care is needed where the GP is considered part of the treating team. Early involvement of GPs and two-way communication between hospital and primary care during the disease continuum is required for this to occur.