RT Journal Article
SR Electronic
T1 Alternative Promoters Drive Human Cytomegalovirus Reactivation from Latency
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 484436
DO 10.1101/484436
A1 Donna Collins-McMillen
A1 Mike Rak
A1 Jason Buehler
A1 Suzu Igarashi-Hayes
A1 Jeremy Kamil
A1 Nat Moorman
A1 Felicia Goodrum
YR 2018
UL http://biorxiv.org/content/early/2018/12/01/484436.abstract
AB 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 is poorly active in HPCs, it is unclear how viral transactivators are expressed during reactivation. We demonstrate that transcripts originating from alternative promoters within the canonical major immediate early locus are abundantly expressed upon reactivation, whereas MIEP-derived transcripts remain undetectable. Further, we show that these promoters are necessary for efficient reactivation in primary CD34+ HPCs. Our findings change the paradigm for HCMV reactivation by demonstrating that promoter switching governs reactivation from viral latency in a context-specific manner.