Ectopic expression of HCMV IE72 and IE86 proteins is sufficient to induce early gene expression but not production of infectious virus in undifferentiated promonocytic THP-1 cells

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Abstract

Human cytomegalovirus (HCMV) reactivation from latency causes disease in individuals who are immunocompromised or immunosuppressed. Activation of the major immediate-early (MIE) promoter is thought to be an initial step for reactivation. We determined whether expression of the MIE gene products in trans was sufficient to circumvent an HCMV latent-like state in an undifferentiated transformed human promonocytic (THP)-1 cell model system. Expression of the functional MIE proteins was achieved with a replication-defective adenovirus vector, Ad-IE1/2, which contains the MIE gene locus. Expression of the MIE proteins by Ad-IE1/2 prior to HCMV infection induced viral early gene expression accompanied by an increase in active chromatin signals. Expression of the anti-apoptotic protein encoded by UL37x1 increased viral early gene expression. However, viral DNA replication and production of infectious virus was not detected. As expected, cellular differentiation with phorbol 12-myristate 13-acetate and hydrocortisone induced virus production. Cellular differentiation is required for efficient viral reactivation. © 2007 Elsevier Inc. All rights reserved.

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Yee, L. F., Lin, P. L., & Stinski, M. F. (2007). Ectopic expression of HCMV IE72 and IE86 proteins is sufficient to induce early gene expression but not production of infectious virus in undifferentiated promonocytic THP-1 cells. Virology, 363(1), 174–188. https://doi.org/10.1016/j.virol.2007.01.036

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