A Zika virus primary isolate induces neuroinflammation, compromises the blood‐brain barrier and upregulates CXCL12 in adult macaques

• Published in: Brain pathology (Zurich, Switzerland) Vol. 30; no. 6; pp. 1017 - 1027
• Main Authors: Panganiban, Antonito T., Blair, Robert V., Hattler, Julian B., Bohannon, Diana G., Bonaldo, Myrna C., Schouest, Blake, Maness, Nicholas J., Kim, Woong‐Ki
• Format: Journal Article
• Language: English
• Published: Switzerland John Wiley & Sons, Inc 01-11-2020; John Wiley and Sons Inc
• Subjects: Adults; Blood; Blood-brain barrier; Brain; Central nervous system; Chemokines; CXCL12; CXCL12 protein; Fetuses; flavivirus; Infections; Inflammation; Lymphocytes; Myelination; Neuropathogenesis; Neuropathology; nonhuman primate; Pregnancy; Viral infections; Viruses; Zika virus; blood-brain barrier; Zika virus; nonhuman primate; CXCL12; flavivirus
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/bpa.12873

Zika virus (ZIKV) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. We used a nonhuman primate model, the Indian‐origin Rhesus macaque (IRM), to gain insight into virus‐associated hallmarks of ZIKV‐induced adult neuropathology. We find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood‐brain barrier (BBB) in adult animals. ZIKV infection resulted in specific short‐ and long‐term augmented expression of the chemokine CXCL12 in the central nervous system (CNS)of adult IRMs. Moreover, CXCL12 expression persists long after the initial viral infection is apparently cleared. CXCL12 plays a key role both in regulating lymphocyte trafficking through the BBB to the CNS and in mediating repair of damaged neural tissue including remyelination. Understanding how CXCL12 expression is controlled will likely be of central importance in the definition of ZIKV‐associated neuropathology in adults.