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

Publication date: Available online 27 April 2017
Source:Cell
Author(s): Malika Aid, Peter Abbink, Rafael A. Larocca, Michael Boyd, Ramya Nityanandam, Ovini Nanayakkara, Amanda J. Martinot, Edward T. Moseley, Eryn Blass, Erica N. Borducchi, Abishek Chandrashekar, Amanda L. Brinkman, Katherine Molloy, David Jetton, Lawrence J. Tartaglia, Jinyan Liu, Katharine Best, Alan S. Perelson, Rafael A. De La Barrera, Mark G. Lewis, Dan H. Barouch
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.

Graphical abstract

Teaser

Persistence of Zika virus in the CNS and lymphoid tissues of NHPs suggests that ZIKV infection may have consequences to humans beyond the reported birth defects.


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