PMID- 28068513
OWN - NLM
STAT- MEDLINE
DCOM- 20170529
LR  - 20191008
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 503
DP  - 2017 Mar
TI  - Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits 
      Zika virus replication.
PG  - 1-5
LID - S0042-6822(16)30400-7 [pii]
LID - 10.1016/j.virol.2016.12.019 [doi]
AB  - We identified primary human monocyte-derived macrophages (MDM) as vulnerable 
      target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of 
      hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), 
      in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells 
      and primary MDM exhibited hemin-induced HO-1 expression with major reductions of 
      >90% in ZIKV replication, with little toxicity to infected cells. Silencing 
      expression of HO-1 or its upstream regulatory gene, nuclear factor 
      erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV 
      infection, suggesting an important role for induction of these intracellular 
      mediators in retarding ZIKV replication. The inverse correlation between 
      hemin-induced HO-1 levels and ZIKV replication provides a potentially useful 
      therapeutic modality based on stimulation of an innate cellular response against 
      Zika virus infection.
CI  - Published by Elsevier Inc.
FAU - Huang, Hanxia
AU  - Huang H
AD  - Food and Drug Administration, Silver Spring, MD, United States.
FAU - Falgout, Barry
AU  - Falgout B
AD  - Food and Drug Administration, Silver Spring, MD, United States.
FAU - Takeda, Kazuyo
AU  - Takeda K
AD  - Food and Drug Administration, Silver Spring, MD, United States.
FAU - Yamada, Kenneth M
AU  - Yamada KM
AD  - National Institutes of Health, Bethesda, MD, United States.
FAU - Dhawan, Subhash
AU  - Dhawan S
AD  - Food and Drug Administration, Silver Spring, MD, United States. Electronic 
      address: subhash.dhawan@fda.hhs.gov.
LA  - eng
GR  - Z01 DE000524-17/Intramural NIH HHS/United States
GR  - Z99 DE999999/Intramural NIH HHS/United States
GR  - Z01 DE000524-18/Intramural NIH HHS/United States
GR  - FD999999/Intramural FDA HHS/United States
GR  - Z01 DE000525-17/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20170106
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 743LRP9S7N (Hemin)
RN  - EC 1.14.14.18 (HMOX1 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Cells, Cultured
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Hemin/*pharmacology
MH  - Humans
MH  - Immunity, Innate/immunology
MH  - Macrophages/immunology/*virology
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - Virus Replication/*drug effects/immunology
MH  - Zika Virus/*immunology
MH  - Zika Virus Infection/*drug therapy/virology
PMC - PMC5325777
MID - NIHMS842234
OTO - NOTNLM
OT  - Heme oxygenase-1
OT  - Macrophages
OT  - Monocytes
OT  - Nuclear factor erythroid-related factor 2
OT  - Zika
EDAT- 2017/01/10 06:00
MHDA- 2017/05/30 06:00
PMCR- 2017/03/01
CRDT- 2017/01/10 06:00
PHST- 2016/09/22 00:00 [received]
PHST- 2016/12/15 00:00 [revised]
PHST- 2016/12/18 00:00 [accepted]
PHST- 2017/01/10 06:00 [pubmed]
PHST- 2017/05/30 06:00 [medline]
PHST- 2017/01/10 06:00 [entrez]
PHST- 2017/03/01 00:00 [pmc-release]
AID - S0042-6822(16)30400-7 [pii]
AID - 10.1016/j.virol.2016.12.019 [doi]
PST - ppublish
SO  - Virology. 2017 Mar;503:1-5. doi: 10.1016/j.virol.2016.12.019. Epub 2017 Jan 6.