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Nipah virus persists in the brains of nonhuman primate survivors
Jun Liu, … , Jens H. Kuhn, Xiankun Zeng
Jun Liu, … , Jens H. Kuhn, Xiankun Zeng
Published July 25, 2019
Citation Information: JCI Insight. 2019;4(14):e129629. https://doi.org/10.1172/jci.insight.129629.
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Research Article Infectious disease Virology

Nipah virus persists in the brains of nonhuman primate survivors

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Abstract

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes highly lethal henipavirus encephalitis in humans. Survivors develop various neurologic sequelae, including late-onset and relapsing encephalitis, several months up to several years following initial infection. However, the underlying pathology and disease mechanisms of persistent neurologic complications remain unknown. Here, we demonstrate persistent NiV infection in the brains of grivets that survived experimental exposure to NiV. Encephalitis affected the entire brains, with the majority of NiV detected in the neurons and microglia of the brainstems, cerebral cortices, and cerebella. We identified the vascular endothelium in the brain as an initial target of NiV infection during the acute phase of disease, indicating a primary path of entry for NiV into the brain. Notably, we were unable to detect NiV anywhere else except the brains in the examined survivors. Our findings indicate that late-onset and relapsing encephalitis of NiV in human survivors may be due to viral persistence in the brain and shed light on the pathogenesis of chronic henipavirus encephalitis.

Authors

Jun Liu, Kayla M. Coffin, Sara C. Johnston, April M. Babka, Todd M. Bell, Simon Y. Long, Anna N. Honko, Jens H. Kuhn, Xiankun Zeng

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Figure 1

NiV persists in the brains of grivet survivors.

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NiV persists in the brains of grivet survivors.
(A) NiV genomic RNA in P...
(A) NiV genomic RNA in PBMCs of survivor 1 and survivor 2 was determined by reverse transcriptase quantitative PCR (RT-qPCR). No viral RNA was detected in either survivor on study day 32. (B–D) Compared with an uninfected grivet control brain (B), genomic NiV RNA (detected by ISH, red) is present multifocally in hematoxylin-stained (blue) FFPE brain sections (C, cerebral cortex; D, brainstem) of grivet survivors. (E) Schematic illustration of persistent NiV infection (red dots, viral RNA by ISH) mainly in brainstem and cerebellum in addition to cerebral cortex. (F and G) Compared with uninfected grivet control brain (F), both NiV genome (red) and antigenome/mRNA (green) are present in the brain using mFISH (G). Nuclei are stained blue (DAPI). (H–J) Compared with uninfected grivet control brain (H), NiV antigen (IHC, brown) is present in hematoxylin-stained (blue) brain sections of grivet survivors (I and J). Scale bars: 50 μm (B–D and H–J), 10 μm (F and G).

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