4.5 Article

Modeling neuro-immune interactions during Zika virus infection

Journal

HUMAN MOLECULAR GENETICS
Volume 27, Issue 1, Pages 41-52

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddx382

Keywords

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Funding

  1. California Institute for Regenerative Medicine [DISC2-09649]
  2. National Institutes of Health [U19MH107367]
  3. Zika Network FAPESP projects [2011/18703-2, 2014/17766-9]
  4. NGO the tooth fairy project
  5. A.P. Giannini Foundation
  6. NARSAD Independent Investigator Grant
  7. NATIONAL INSTITUTE OF MENTAL HEALTH [U19MH107367] Funding Source: NIH RePORTER

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Although Zika virus (ZIKV) infection is often asymptomatic, in some cases, it can lead to birth defects in newborns or serious neurologic complications in adults. However, little is known about the interplay between immune and neural cells that could contribute to the ZIKV pathology. To understand the mechanisms at play during infection and the antiviral immune response, we focused on neural precursor cells (NPCs)-microglia interactions. Our data indicate that human microglia infected with the current circulating Brazilian ZIKV induces a similar pro-inflammatory response found in ZIKV-infected human tissues. Importantly, using our model, we show that microglia interact with ZIKV-infected NPCs and further spread the virus. Finally, we show that Sofosbuvir, an FDA-approved drug for Hepatitis C, blocked viral infection in NPCs and therefore the transmission of the virus from microglia to NPCs. Thus, our model provides a new tool for studying neuro-immune interactions and a platform to test new therapeutic drugs.

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