Modeling neuro-immune interactions during Zika virus infection

Author(s)

Mesci, Pinar ^{[1, 2]} ; Macia, Angela ^{[1, 2]} ; LaRock, Christopher N. ^{[3, 4]} ; Tejwani, Leon ^{[1, 2]} ; Fernandes, Isabella R. ^{[1, 2]} ; Suarez, Nicole A. ^{[1, 2]} ; Zanotto, Paolo M. de A. ^[5] ; Beltrao-Braga, Patricia C. B. ^{[6, 7, 8]} ; Nizet, Victor ^{[3, 4]} ; Muotri, Alysson R. ^{[1, 2]}

Affiliation

^[1] Univ Calif San Diego, Sch Med, Dept Pediat, Rady Childrens Hosp San Diego, La Jolla, CA 92093 - USA

^[2] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, Stem Cell Program, La Jolla, CA 92093 - USA

^[3] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 - USA

^[4] Univ Calif San Diego, Sch Med, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 - USA

^[5] Univ Sao Paulo, Inst Microbiol Sci, Dept Microbiol, Lab Mol Evolut & Bioinformat, BR-05508000 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Stem Cell & Dis Modeling, BR-05508000 Sao Paulo, SP - Brazil

^[7] Univ Sao Paulo, Sch Arts Sci & Humanities, Dept Obstet, BR-03828000 Sao Paulo, SP - Brazil

^[8] Univ Sao Paulo, Sch Med, Ctr Cellular & Mol Therapy NETCEM, BR-01246903 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Human Molecular Genetics; v. 27, n. 1, p. 41-52, JAN 1 2018.
• Web of Science Citations: 17

Abstract

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. (AU)

• FAPESP's process: 14/17766-9 - A systemic approach to study permissivity on the Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV)
• Grantee: Paolo Marinho de Andrade Zanotto
• Support type: Regular Research Grants
• FAPESP's process: 11/18703-2 - The role of Indoleamine-2,3-dioxigenase and the Triptophan - Kynurenines axis through NMDA receptors over the immune response in the EAE and stroke model
• Grantee: Jean Pierre Schatzmann Peron
• Support type: Research Grants - Young Investigators Grants