Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells

Krishna, B.A., Lau, B. , Jackson, S.E., Wills, M.R., Sinclair, J.H. and Poole, E. (2016) Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells. Scientific Reports, 6, 24674. (doi: 10.1038/srep24674) (PMID:27091512) (PMCID:PMC4835774)

Abstract

Human cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lau, Dr Betty
• Authors: Krishna, B.A., Lau, B., Jackson, S.E., Wills, M.R., Sinclair, J.H., and Poole, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Scientific Reports
• Publisher: Nature Publishing Group
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Scientific Reports 6:24674
• Publisher Policy: Reproduced under a Creative Commons License