Alternative promoters drive human cytomegalovirus reactivation from latency

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Arizona
  • Renascent Biosciences
  • University of North Carolina at Chapel Hill

Details

Original languageEnglish (US)
Pages (from-to)17492-17497
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number35
StatusPublished - Aug 27 2019
Peer-reviewedYes

Abstract

Reactivation from latency requires reinitiation of viral gene expression and culminates in the production of infectious progeny. The major immediate early promoter (MIEP) of human cytomegalovirus (HCMV) drives the expression of crucial lytic cycle transactivators but is silenced during latency in hematopoietic progenitor cells (HPCs). Because the MIEP has poor activity in HPCs, it is unclear how viral transactivators are expressed during reactivation. It has been presumed that viral gene expression is reinitiated via de-repression of the MIEP. We demonstrate that immediate early transcripts arising from reactivation originate predominantly from alternative promoters within the canonical major immediate early locus. Disruption of these intronic promoters results in striking defects in re-expression of viral genes and viral genome replication in the THP-1 latency model. Furthermore, we show that these promoters are necessary for efficient reactivation in primary CD34+ HPCs. Our findings shift the paradigm for HCMV reactivation by demonstrating that promoter switching governs reactivation from viral latency in a context-specific manner.

    Research areas

  • Human cytomegalovirus, Latency, Reactivation

Citation formats

APA

Collins-McMillen, D., Rak, M., Buehler, J. C., Igarashi-Hayes, S., Kamil, J. P., Moorman, N. J., & Goodrum, F. (2019). Alternative promoters drive human cytomegalovirus reactivation from latency. Proceedings of the National Academy of Sciences of the United States of America, 116(35), 17492-17497. https://doi.org/10.1073/pnas.1900783116

Harvard

Collins-McMillen, D, Rak, M, Buehler, JC, Igarashi-Hayes, S, Kamil, JP, Moorman, NJ & Goodrum, F 2019, 'Alternative promoters drive human cytomegalovirus reactivation from latency', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 35, pp. 17492-17497. https://doi.org/10.1073/pnas.1900783116