TY - JOUR
T1 - Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency
AU - Alfonso-Dunn, Roberto
AU - Turner, Anne Marie W.
AU - Jean Beltran, Pierre M.
AU - Arbuckle, Jesse H.
AU - Budayeva, Hanna G.
AU - Cristea, Ileana M.
AU - Kristie, Thomas M.
N1 - Funding Information:
We thank J. Vogel (Laboratory of Viral Diseases, NIAID) for discussions and review of this manuscript, A. McBride and M.K. Jang (Laboratory of Viral Diseases, NIAID) for BRD reagents, and NIAID Bld33 Vivarium staff and A. Reed (Laboratory of Viral Diseases, NIAID) for excellent technical support. This study was supported by the Intramural Research Program of the NIH, NIAID (T.M.K.), the Mallinckrodt Scholar Award (I.M.C.), and NIGMS (GM114141, I.M.C.).
Publisher Copyright:
© 2017
PY - 2017/4/12
Y1 - 2017/4/12
N2 - The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the super elongation complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation, and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs. Significantly, compounds that enhance the levels of SEC-P-TEFb also potently stimulated HSV reactivation from latency both in a sensory ganglia model system and in vivo. Thus, transcriptional elongation of HSV IE genes is a key limiting parameter governing both the initiation of HSV infection and reactivation of latent genomes.
AB - The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the super elongation complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation, and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs. Significantly, compounds that enhance the levels of SEC-P-TEFb also potently stimulated HSV reactivation from latency both in a sensory ganglia model system and in vivo. Thus, transcriptional elongation of HSV IE genes is a key limiting parameter governing both the initiation of HSV infection and reactivation of latent genomes.
KW - P-TEFb
KW - herpes simplex virus
KW - host cell factor-1
KW - latency
KW - super elongation complex
KW - transcriptional elongation
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U2 - 10.1016/j.chom.2017.03.007
DO - 10.1016/j.chom.2017.03.007
M3 - Article
C2 - 28407486
AN - SCOPUS:85017388724
SN - 1931-3128
VL - 21
SP - 507-517.e5
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -