PMID- 26468534
OWN - NLM
STAT- MEDLINE
DCOM- 20160426
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 1
DP  - 2016 Jan 1
TI  - Kaposi's Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation 
      Primary-Response Gene 88 (MyD88) Expression via Modulation of Its RNA.
PG  - 180-8
LID - 10.1128/JVI.02342-15 [doi]
AB  - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus 
      associated with several human malignancies. The replication and transcription 
      activator (RTA) is necessary and sufficient for the switch from KSHV latency to 
      lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and 
      plays an important role in both innate and adaptive immunity. Myeloid 
      differentiation primary response gene 88 (MyD88) is an essential adaptor molecule 
      for IL-1 as well as most Toll-like receptor signaling. In this study, we 
      identified a novel mechanism by which KSHV interferes with host inflammation and 
      immunity. KSHV RTA specifically reduces the steady-state protein levels of MyD88, 
      and physiological levels of MyD88 are downregulated during KSHV lytic replication 
      when RTA is expressed. The N-terminal region of RTA is required for the reduction 
      of MyD88. Additional studies demonstrated that RTA targets MyD88 expression at 
      the RNA level, inhibits RNA synthesis of MyD88, and may bind MyD88 RNA. Finally, 
      RTA inhibits IL-1-mediated activation of NF-kappaB. Because IL-1 is abundant in the 
      KS microenvironment and inhibits KSHV replication, this work may expand our 
      understanding of how KSHV evades host inflammation and immunity for its survival 
      in vivo. IMPORTANCE: MyD88 is an important molecule for IL-1-mediated 
      inflammation and Toll-like receptor (TLR) signaling. This work shows that KSHV 
      inhibits MyD88 expression through a novel mechanism. KSHV RTA may bind to MyD88 
      RNA, suppresses RNA synthesis of MyD88, and inhibits IL-1-mediated signaling. 
      This work may expand our understanding of how KSHV evades host inflammation and 
      immunity.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Lingel, Amy
AU  - Lingel A
AD  - School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA.
FAU - Ehlers, Erica
AU  - Ehlers E
AD  - School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA.
FAU - Wang, Qianli
AU  - Wang Q
AD  - School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA.
FAU - Cao, Mingxia
AU  - Cao M
AD  - School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA.
FAU - Wood, Charles
AU  - Wood C
AD  - School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA 
      Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, USA.
FAU - Lin, Rongtuan
AU  - Lin R
AD  - Lady Davis Institute for Medical Research, Department of Medicine, McGill 
      University, Montreal, Quebec, Canada.
FAU - Zhang, Luwen
AU  - Zhang L
AD  - School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA 
      Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, USA 
      lzhang2@unl.edu.
LA  - eng
GR  - CA138213/CA/NCI NIH HHS/United States
GR  - R01 CA138213/CA/NCI NIH HHS/United States
GR  - RR15635/RR/NCRR NIH HHS/United States
GR  - P30 GM103509/GM/NIGMS NIH HHS/United States
GR  - P20 RR015635/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151014
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rta protein, Human herpesvirus 8)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Cell Line
MH  - *Down-Regulation
MH  - Herpesvirus 8, Human/*immunology/*physiology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Immediate-Early Proteins/*metabolism
MH  - Immune Evasion
MH  - Interleukin-1/antagonists & inhibitors
MH  - Myeloid Differentiation Factor 88/antagonists & inhibitors/*biosynthesis
MH  - NF-kappa B/antagonists & inhibitors
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - RNA, Messenger/metabolism
MH  - Trans-Activators/*metabolism
PMC - PMC4702530
EDAT- 2015/10/16 06:00
MHDA- 2016/04/27 06:00
PMCR- 2016/06/17
CRDT- 2015/10/16 06:00
PHST- 2015/09/11 00:00 [received]
PHST- 2015/10/02 00:00 [accepted]
PHST- 2015/10/16 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2016/04/27 06:00 [medline]
PHST- 2016/06/17 00:00 [pmc-release]
AID - JVI.02342-15 [pii]
AID - 02342-15 [pii]
AID - 10.1128/JVI.02342-15 [doi]
PST - epublish
SO  - J Virol. 2015 Oct 14;90(1):180-8. doi: 10.1128/JVI.02342-15. Print 2016 Jan 1.