Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1-infected human macrophages.

Boliar, Saikat, Gludish, David W, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Kamng'ona, Raphael, Mvaya, Leonard, Mwandumba, Henry ORCID: https://orcid.org/0000-0003-4470-3608 and Russell, David (2019) 'Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1-infected human macrophages.'. Proceedings of the National Academy of Sciences of the United States of America, Vol 116, Issue 15, pp. 7431-7438.

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Abstract

Long noncoding RNAs (lncRNAs) impart significant regulatory functions in a diverse array of biological pathways and manipulation of these RNAs provides an important avenue to modulate such pathways, particularly in disease. Our knowledge about lncRNAs' role in determination of cellular fate during HIV-1 infection remains sparse. Here, we have identified the impact of the lncRNA SAF in regulating apoptotic effector caspases in macrophages, a long-lived cellular reservoir of HIV-1, that are largely immune to virus-induced cell death. Expression of SAF is significantly up-regulated in HIV-1-infected human monocyte-derived macrophages (MDM) compared with bystander and virus-nonexposed cells. A similar enhancement in SAF RNA expression is also detected in the HIV-1-infected airway macrophages obtained by bronchoalveolar lavage of HIV-1-infected individuals. Down-regulation of SAF with siRNA treatment increases caspase-3/7 activity levels in virus-infected MDMs. This induction of apoptotic caspases occurs exclusively in HIV-1-infected macrophages and not in bystander cells, leading to a significant reduction in HIV-1 replication and overall viral burden in the macrophage culture. This study identifies targeting of the lncRNA SAF as a potential means to specifically induce cell death in HIV-1-infected macrophages.

Item Type:	Article
Subjects:	WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General) WH Hemic and Lymphatic Systems > Lymphatic System > WH 650 Reticuloendothelial system
Faculty: Department:	Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.1818662116
Depositing User:	Stacy Murtagh
Date Deposited:	04 Apr 2019 14:23
Last Modified:	13 Dec 2019 15:36
URI:	https://archive.lstmed.ac.uk/id/eprint/10559

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