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.
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.
Yee
Lian-Fai
LF
3-701 BSB, 51 Newton Road, Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Lin
Philip L
PL
Stinski
Mark F
MF
D000256:Adenoviridae / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D004279:DNA, Viral; C088645:IE1 protein, cytomegalovirus; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D012367:RNA, Viral; D015534:Trans-Activators; C420323:UL37 protein, Human herpesvirus 5; D014764:Viral Proteins