Long and short isoforms of the human cytomegalovirus UL138 protein silence IE transcription and promote latency

Song Hee Lee, Katie Caviness, Emily R. Albright, Jeong Hee Lee, Christopher B. Gelbmann, Mike Rak, Felicia Goodrum, Robert F. Kalejta

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The UL133-138 locus present in clinical strains of human cytomegalovirus (HCMV) encodes proteins required for latency and reactivation in CD34+ hematopoietic progenitor cells and virion maturation in endothelial cells. The encoded proteins form multiple homo- and hetero-interactions and localize within secretory membranes. One of these genes, UL136 gene, is expressed as at least five different protein isoforms with overlapping and unique functions. Here we show that another gene from this locus, the UL138 gene, also generates more than one protein isoform. A long form of UL138 (pUL138-L) initiates translation from codon 1, possesses an amino-terminal signal sequence, and is a type one integral membrane protein. Here we identify a short protein isoform (pUL138-S) initiating from codon 16 that displays a subcellular localization similar to that of pUL138-L. Reporter, short-term transcription, and long-term virus production assays revealed that both pUL138-L and pUL138-S are able to suppress major immediate early (IE) gene transcription and the generation of infectious virions in cells in which HCMV latency is studied. The long form appears to be more potent at silencing IE transcription shortly after infection, while the short form seems more potent at restricting progeny virion production at later times, indicating that both isoforms of UL138 likely cooperate to promote HCMV latency.

Original languageEnglish (US)
Pages (from-to)9483-9494
Number of pages12
JournalJournal of Virology
Volume90
Issue number20
DOIs
StatePublished - 2016

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Immediate-Early Proteins
Human herpesvirus 5
Cytomegalovirus
Protein Isoforms
protein isoforms
transcription (genetics)
Virion
virion
Codon
Genes
genes
proteins
codons
Genetic Transcription
Immediate-Early Genes
Protein Sorting Signals
Hematopoietic Stem Cells
loci
Homo
Membrane Proteins

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Lee, S. H., Caviness, K., Albright, E. R., Lee, J. H., Gelbmann, C. B., Rak, M., ... Kalejta, R. F. (2016). Long and short isoforms of the human cytomegalovirus UL138 protein silence IE transcription and promote latency. Journal of Virology, 90(20), 9483-9494. https://doi.org/10.1128/JVI.01547-16

Long and short isoforms of the human cytomegalovirus UL138 protein silence IE transcription and promote latency. / Lee, Song Hee; Caviness, Katie; Albright, Emily R.; Lee, Jeong Hee; Gelbmann, Christopher B.; Rak, Mike; Goodrum, Felicia; Kalejta, Robert F.

In: Journal of Virology, Vol. 90, No. 20, 2016, p. 9483-9494.

Research output: Contribution to journalArticle

Lee, SH, Caviness, K, Albright, ER, Lee, JH, Gelbmann, CB, Rak, M, Goodrum, F & Kalejta, RF 2016, 'Long and short isoforms of the human cytomegalovirus UL138 protein silence IE transcription and promote latency', Journal of Virology, vol. 90, no. 20, pp. 9483-9494. https://doi.org/10.1128/JVI.01547-16
Lee, Song Hee ; Caviness, Katie ; Albright, Emily R. ; Lee, Jeong Hee ; Gelbmann, Christopher B. ; Rak, Mike ; Goodrum, Felicia ; Kalejta, Robert F. / Long and short isoforms of the human cytomegalovirus UL138 protein silence IE transcription and promote latency. In: Journal of Virology. 2016 ; Vol. 90, No. 20. pp. 9483-9494.
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