PMID- 28457610
OWN - NLM
STAT- MEDLINE
DCOM- 20170703
LR  - 20231112
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 169
IP  - 4
DP  - 2017 May 4
TI  - Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus 
      Monkeys.
PG  - 610-620.e14
LID - S0092-8674(17)30421-X [pii]
LID - 10.1016/j.cell.2017.04.008 [doi]
AB  - Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as 
      Guillain-Barre syndrome and other neurologic disorders in adults. Prolonged viral 
      shedding has been reported in semen, suggesting the presence of anatomic viral 
      reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and 
      lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been 
      cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific 
      neutralizing antibodies correlated with rapid clearance of virus in peripheral 
      blood but remained undetectable in CSF for the duration of the study. Viral 
      persistence in both CSF and LN correlated with upregulation of mechanistic target 
      of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as 
      well as downregulation of extracellular matrix signaling pathways. These data 
      raise the possibility that persistent or occult neurologic and lymphoid disease 
      may occur following clearance of peripheral virus in ZIKV-infected individuals.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Aid, Malika
AU  - Aid M
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Abbink, Peter
AU  - Abbink P
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Larocca, Rafael A
AU  - Larocca RA
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Boyd, Michael
AU  - Boyd M
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Nityanandam, Ramya
AU  - Nityanandam R
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Nanayakkara, Ovini
AU  - Nanayakkara O
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Martinot, Amanda J
AU  - Martinot AJ
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Moseley, Edward T
AU  - Moseley ET
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Blass, Eryn
AU  - Blass E
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Borducchi, Erica N
AU  - Borducchi EN
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Chandrashekar, Abishek
AU  - Chandrashekar A
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Brinkman, Amanda L
AU  - Brinkman AL
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Molloy, Katherine
AU  - Molloy K
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Jetton, David
AU  - Jetton D
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Tartaglia, Lawrence J
AU  - Tartaglia LJ
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Liu, Jinyan
AU  - Liu J
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA.
FAU - Best, Katharine
AU  - Best K
AD  - Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
FAU - Perelson, Alan S
AU  - Perelson AS
AD  - Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
FAU - De La Barrera, Rafael A
AU  - De La Barrera RA
AD  - Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
FAU - Lewis, Mark G
AU  - Lewis MG
AD  - Bioqual, Rockville, MD 20852, USA.
FAU - Barouch, Dan H
AU  - Barouch DH
AD  - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and 
      Harvard, Cambridge, MA 02139, USA. Electronic address: 
      dbarouch@bidmc.harvard.edu.
LA  - eng
GR  - R01 OD011095/OD/NIH HHS/United States
GR  - UM1 AI100663/AI/NIAID NIH HHS/United States
GR  - U19 AI095985/AI/NIAID NIH HHS/United States
GR  - R01 AI028433/AI/NIAID NIH HHS/United States
GR  - U19 AI096040/AI/NIAID NIH HHS/United States
GR  - R01 AI078881/AI/NIAID NIH HHS/United States
GR  - R56 AI078881/AI/NIAID NIH HHS/United States
GR  - UM1 AI124377/AI/NIAID NIH HHS/United States
GR  - UM1 AI126603/AI/NIAID NIH HHS/United States
GR  - R37 AI028433/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170427
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cerebrospinal Fluid/virology
MH  - Inflammation/immunology
MH  - Lower Gastrointestinal Tract/virology
MH  - Lymph Nodes/virology
MH  - Macaca mulatta
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Zika Virus Infection/*immunology/*virology
PMC - PMC5426912
MID - NIHMS867729
OTO - NOTNLM
OT  - CSF
OT  - Zika
OT  - infection
OT  - lymph node
OT  - mTOR
OT  - persistence
OT  - rhesus
OT  - sanctuaries
OT  - transcriptomics
OT  - viral dynamics
COIS- The authors declare no competing financial interests.
EDAT- 2017/05/02 06:00
MHDA- 2017/07/04 06:00
PMCR- 2018/05/04
CRDT- 2017/05/02 06:00
PHST- 2016/12/05 00:00 [received]
PHST- 2017/03/12 00:00 [revised]
PHST- 2017/04/06 00:00 [accepted]
PHST- 2017/05/02 06:00 [pubmed]
PHST- 2017/07/04 06:00 [medline]
PHST- 2017/05/02 06:00 [entrez]
PHST- 2018/05/04 00:00 [pmc-release]
AID - S0092-8674(17)30421-X [pii]
AID - 10.1016/j.cell.2017.04.008 [doi]
PST - ppublish
SO  - Cell. 2017 May 4;169(4):610-620.e14. doi: 10.1016/j.cell.2017.04.008. Epub 2017 
      Apr 27.