Abstract：
:Human cytomegalovirus (HCMV) establishes life-long latent infection in hematopoietic progenitor cells and circulating monocytes in infected individuals. Myeloid differentiation coupled with immune dysregulation leads to viral reactivation, which can cause severe disease and mortality. Reactivation of latent virus requires chromatin reorganization and the removal of transcriptional repressors in exchange for transcriptional activators. While some factors involved in these processes are identified, a complete characterization of the viral and cellular factors involved in their upstream regulation remains elusive. Herein, we show the HCMV-encoded G protein-coupled receptor (GPCR), UL33, is expressed during latency. Although this viral GPCR is not required to maintain latent infection, our data reveal UL33-mediated signaling is important for efficient viral reactivation. Additionally, UL33 signaling induces cellular cyclic AMP response element binding protein (CREB1, referred to here as CREB) phosphorylation, a transcription factor that promotes reactivation when recruited to the major immediate early (MIE) enhancer/promoter. Finally, targeted pharmacological inhibition of CREB activity reverses the reactivation phenotype of the UL33 signaling-deficient mutant. In sum, our data reveal UL33-mediated signaling functions to activate CREB, resulting in successful viral reactivation.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Krishna BA,Wass AB,Dooley AL,O'Connor CMdoi
10.1242/jcs.254268subject
Has Abstractpub_date
2021-01-25 00:00:00issue
5eissn
0021-9533issn
1477-9137pii
jcs.254268journal_volume
134pub_type
杂志文章abstract：:The mammalian lens consists of an aged core of quiescent cells enveloped by a layer of synthetically active cells. Abundant gap junctions within and between these cell populations ensure that the lens functions as an electrical syncytium and facilitates the exchange of small molecules between surface and core cells. I...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00738
更新日期：2003-10-15 00:00:00
abstract：:The molecular mechanisms regulating skeletal muscle regeneration and differentiation are not well understood. We analyzed the expression of connexins (Cxs) 40, 43 and 45 in normal and regenerating tibialis anterior muscle and in primary cultures of differentiating myoblasts in adult and newborn mice, respectively. Cxs...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01553
更新日期：2005-01-01 00:00:00
abstract：:Cytostellin, a approximately 240 kDa phosphoprotein found in all cells examined from human to yeast, is predominantly intranuclear in interphase mammalian cells and undergoes continuous redistribution during the cell cycle. Here, mammalian cytostellin is shown to localize to intranuclear regions enriched with multiple...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Desmoplakin is an intracellular component of desmosomes which plays a role in the anchorage of intermediate filaments to these structures. We report here that, despite the absence of desmosomes, cultured endothelial cells from human umbilical vein express desmoplakin I and II both at mRNA and protein level. Desmoplaki...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
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journal_title：Journal of cell science
pub_type： 杂志文章
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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doi：
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doi：10.1242/jcs.046805
更新日期：2009-06-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.013557
更新日期：2008-02-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02450
更新日期：2005-08-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.212548
更新日期：2018-03-06 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：2012-03-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.210724
更新日期：2018-05-08 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
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journal_title：Journal of cell science
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更新日期：2013-02-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
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journal_title：Journal of cell science
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doi：
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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doi：
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journal_title：Journal of cell science
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doi：
更新日期：1999-05-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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更新日期：1980-08-01 00:00:00
