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Cell. 2017 May 4;169(4):610-620.e14. doi: 10.1016/j.cell.2017.04.008. Epub 2017 Apr 27.

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
2
Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
3
Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
4
Bioqual, Rockville, MD 20852, USA.
5
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.

Abstract

Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barré 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.

KEYWORDS:

CSF; Zika; infection; lymph node; mTOR; persistence; rhesus; sanctuaries; transcriptomics; viral dynamics

PMID:
28457610
PMCID:
PMC5426912
DOI:
10.1016/j.cell.2017.04.008
[Indexed for MEDLINE]
Free PMC Article

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